1. The Ca(2+)-antagonistic properties of lacidipine were investigated in patch-clamp guinea-pig ventricular myocytes. 2. In basal conditions, 0.1 microM lacidipine reduced the action potential duration, associated with a decrease in the L-type calcium current (ICa,L) to 66 +/- 4% of the control value, without a change in the current-voltage relationship. Sodium current and background potassium currents were not affected. All the effects reached a steady state within 2 min. 3. The Ca(2+)-antagonistic effect of lacidipine was voltage-dependent: a marked negative shift (about 20 mV) of the steady-state inactivation curve was observed with long (10 s) conditioning prepulses, but not with short (350 ms) prepulses. 4. The onset of and recovery from the voltage-dependent effect caused by 0.1 microM lacidipine were significantly slower when compared to those of equiactive concentrations of nimodipine (0.5 microM) and nisoldipine (0.1 microM). ICa,L measured after prepulses at -40 mV lasting 500 ms or less was unchanged (95 +/- 5% of maximum current value) while it was reduced to 49 +/- 10% by nimodipine and 43 +/- 9% by nisoldipine (P < 0.05 vs lacidipine for both). 5. Similarly, the recovery from block in the presence of lacidipine was slower than with nimodipine and nisoldipine. After a prepulse of 1 s at -80 mV, ICa,L recovered up to 54 +/- 2% of the maximum current value in the presence of lacidipine, and up to 91 +/- 3% and 93 +/- 5% in the presence of nimodipine and nisoldipine, respectively (P < 0.05 vs lacidipine). 6. Blockade of ICa,L by lacidipine was use-dependent. After ten 200 ms long pulses (1 Hz) from -80 mV, ICa,L was reduced to 55 +/- 7% of the current measured at the first pulse. In the presence of nimodipine and nisoldipine, ICa,L elicited by the tenth pulse amounted to 93 +/- 3% and 80 +/- 6% of the first pulse value, respectively (P < 0.05 vs lacidipine). Lacidipine did not cause use-dependent blockade of ICa,L in cells stimulated with 10 ms long pulses. 7. These results demonstrate that lacidipine selectively inhibits ICa,L in isolated cardiomyocytes and suggest that this effect occurs mainly through binding to the inactivated Ca2+ channels.