We have examined the interaction of procaine, prilocaine, lignocaine, bupivacaine, amylocaine and R(+) and S(-) ropivacaine with L-type voltage-sensitive Ca2+ channels in rat cerebrocortical membranes. Membranes were prepared in Tris HCl 50 mmol litre(-1), pH 7.4, by homogenization and centrifugation. Binding assays were performed in 1-ml volumes of Tris HCl 50 mmol litre(-1), pH 7.4, for 90 min at room temperature using approximately 200 mu g of protein. Non-specific binding was defined in the presence of nifedipine 10(-5) mol litre(-1), and bound and free radioactivity were separated by vacuum filtration. The effects of local anaesthetics were determined by displacement of [H-3]PN200-110 (approximately 0.2 nmol litre(-1)), a radiolabelled 1,4-dihydropyridine (DHP) L-channel antagonist. The concentration of displacer producing 50% displacement was corrected for the competing mass of [H-3]PN200-110 to yield the affinity constant, K-50. All local anaesthetics displaced [H-3]PN200-110 in a dose-dependent manner with a rank order potency of (K-50, mmol litre(-1)) bupivacaine (0.48), amylocaine (0.74), lignocaine (1.09), prilocaine (2.06) and procaine (2.09). Ropivacaine enantiomers did not show stereoselective displacement, with K-50 values of 0.99 and 0.92 mmol litre(-1) for R(+) and S(-) ropivacaine, respectively. There was a significant correlation between pK(50) and p (octanol:buffer partition coefficient) (r(2)=0.872, P=0.020), pK(50) and p (local anaesthetic potency) (r(2)=0.816, P=0.036), pK(50) and p (relative conduction blocking potency) (r(2)=0.843, P=0.028) and between pK(50) and p (IC50 for inhibition of cardiac output) (r(2)=0.897, P=0.015). These data suggest that DHP binding sites may be involved in both the mechanism of local anaesthesia and the cardiotoxicity of these agents.