diff --git a/gufe/protocols/protocol.py b/gufe/protocols/protocol.py
index 918e1ba7f..ab30fc206 100644
--- a/gufe/protocols/protocol.py
+++ b/gufe/protocols/protocol.py
@@ -112,7 +112,10 @@ def _from_dict(cls, dct: dict):
 
     @classmethod
     @abc.abstractmethod
-    def _default_settings(cls) -> Settings:
+    def _default_settings(cls, *,
+                          stateA: Optional[ChemicalSystem] = None,
+                          stateB: Optional[ChemicalSystem] = None,
+                          ) -> Settings:
         """Method to override in custom `Protocol` subclasses.
 
         Gives a usable instance of ``Settings`` that function as
@@ -122,14 +125,23 @@ def _default_settings(cls) -> Settings:
         raise NotImplementedError()
 
     @classmethod
-    def default_settings(cls) -> Settings:
+    def default_settings(cls, *,
+                         stateA: Optional[ChemicalSystem] = None,
+                         stateB: Optional[ChemicalSystem] = None,
+                         ) -> Settings:
         """Get the default settings for this `Protocol`.
 
         These can be modified and passed in as the `settings` for a new
         `Protocol` instance.
 
+        Parameters
+        ----------
+        stateA, stateB: ChemicalSystem, optional
+          details of the chemistry that the Protocol will operate on.
+          Depending on implementation, this can be used to fine tune the
+          default settings which are used.
         """
-        return cls._default_settings()
+        return cls._default_settings(stateA=stateA, stateB=stateB)
 
     @abc.abstractmethod
     def _create(
diff --git a/gufe/tests/test_protocol.py b/gufe/tests/test_protocol.py
index 32d3ff885..b4be78678 100644
--- a/gufe/tests/test_protocol.py
+++ b/gufe/tests/test_protocol.py
@@ -97,11 +97,24 @@ class DummyProtocol(Protocol):
     result_cls = DummyProtocolResult
 
     @classmethod
-    def _default_settings(cls):
+    def _default_settings(cls, *,
+                          stateA=None,
+                          stateB=None):
+        repeats = 21
+
+        if stateA and stateB:
+            # we got a hint of the chemistry involved
+            # so inspect and do something clever here
+            # for example if solvent is water we do repeats=21,
+            # otherwise repeats=42
+            sc: gufe.SolventComponent = stateA.components.get('solvent', None)
+            if sc is not None:
+                repeats = 21 if sc.smiles == 'O' else 42
+
         return DummySpecificSettings(
             thermo_settings=settings.ThermoSettings(temperature=298 * unit.kelvin),
             forcefield_settings=settings.OpenMMSystemGeneratorFFSettings(),
-            n_repeats=21,
+            n_repeats=repeats,
         )
 
     @classmethod
@@ -505,7 +518,7 @@ def _defaults(cls):
         return {}
 
     @classmethod
-    def _default_settings(cls):
+    def _default_settings(cls, stateA=None, stateB=None):
         return settings.Settings.get_defaults()
 
     def _create(
@@ -738,3 +751,39 @@ def test_settings_readonly():
         p.settings.thermo_settings.temperature = 400.0 * unit.kelvin
 
     assert p.settings.thermo_settings.temperature == before
+
+
+def test_customised_default_settings():
+    # check that default_settings hook is able to inspect the chemistry to
+    # offer different defaults
+    cs1 = ChemicalSystem(
+        components={
+            'solvent': gufe.SolventComponent(smiles='CC')
+        }
+    )
+    cs2 = ChemicalSystem(
+        components={
+            'solvent': gufe.SolventComponent(smiles='CC')
+        }
+    )
+
+    ds = DummyProtocol.default_settings(stateA=cs1, stateB=cs2)
+
+    assert ds.n_repeats == 42
+
+
+def test_customised_default_settings_defaults():
+    cs1 = ChemicalSystem(
+        components={
+            'solvent': gufe.SolventComponent(smiles='O')
+        }
+    )
+    cs2 = ChemicalSystem(
+        components={
+            'solvent': gufe.SolventComponent(smiles='O')
+        }
+    )
+
+    ds = DummyProtocol.default_settings(stateA=cs1, stateB=cs2)
+
+    assert ds.n_repeats == 21
diff --git a/gufe/tests/test_protocoldag.py b/gufe/tests/test_protocoldag.py
index 9454eda01..bbbaa0dcc 100644
--- a/gufe/tests/test_protocoldag.py
+++ b/gufe/tests/test_protocoldag.py
@@ -41,7 +41,7 @@ class WriterProtocol(gufe.Protocol):
     result_cls = WriterProtocolResult
 
     @classmethod
-    def _default_settings(cls):
+    def _default_settings(cls, stateA=None, stateB=None):
         return WriterSettings(
             thermo_settings=gufe.settings.ThermoSettings(temperature=298 * unit.kelvin),
             forcefield_settings=gufe.settings.OpenMMSystemGeneratorFFSettings(),