The vasodilator (relaxant) action of the antianginal agent bepridil was compared with that of drugs known to either block membrane calcium channels, to be calmodulin antagonists or to inhibit intracellular calcium flux using rat and rabbit aortic strips. IC50 values were obtained for relaxation of tonic contractions induced by either potassium (K+) or phenylephrine (PE). The order of relaxant specificity against K+ compared with PE in both rabbit and rat tissue preparations was nisoldipine = nifedipine greater than diltiazem greater than verapamil greater than bepridil greater than PrMDI greater than W7 greater than TFP greater than phentolamine. The ratio for flunarizine equalled that of bepridil in rabbit and that of verapamil in rat. The calmodulin antagonist TFP showed additional alpha-adrenoceptor blocking properties. Analysis of concentration response curves to the antagonists together with PE/K+ ratios revealed a different profile for each drug tested on rabbit aorta. The range of PE/K+ ratios was much wider in rabbit compared to rat. The results suggest that, with the method used, rabbit aortic strips offer a simple technique for drug profiling and allows a clearer differentiation between membrane active and intracellularly acting drugs than does rat aorta. The profile of bepridil resembled more that of intracellularly acting drugs suggesting that intracellular actions (possibly calmodulin inhibition) may play a substantial role in its dilator actions on vascular smooth muscle.