We have used the whole-cell clamp technique to investigate inactivation of the omega-conotoxin sensitive high-voltage-activated Ca-channel current (HVA current [2]) carried either by Ca, Ba or Sr (2.5 mM) in chick sensory neurons. At a low internal EGTA concentration (0.1 mM), Ca-channel currents clearly inactivated irrespective of the species of divalent cation carrying the current. During 150 ms pulses, current inactivated to 0.57, 0.67 and 0.75 of the peak current in Ca, Ba and Sr solution, respectively. Time constants of inactivation (26 +/- 10 ms and 280 +/- 50 ms, mean +/- S.D., in Ba) were largely independent of the membrane potential. Double-pulse experiments showed that the amount of inactivation left by a pre-pulse was proportional to the amplitude of the current evoked by the pre-pulse. No inactivation was induced by an outward current elicited by a strong depolarization to +60 mV. With an internal EGTA concentration of 20 mM, the amount of inactivation was significantly smaller. In conclusion, the inactivation of the HVA Ca-channel currents during current flow depends mostly on the entry of divalent cations irrespective of their species.