A series of calcium antagonists were used to study their blocking effect on high potassium-induced calcium uptake into rat cortical synaptosomes; these antagonists were classified into five groups: dihydropyridine group (i.e. nifedipine and nitrendipine), benzothiazepine group (i.e. diltiazem), phenylalkylamine group (i.e. verapamil and D600), phenothiazine group (i.e. trifluoperazine) and diphenylpiperazine group (i.e. flunarizine and cinnarizine). Voltage-dependent 45Ca2+-uptake into this fraction was measured after 20 sec KCl-induced depolarization. The ID30 values of the above-mentioned antagonists affecting 45Ca2+-uptake were calculated to be nitrendipine (80 microM), nifedipine (100 microM), verapamil (50 microM), D600 (15 microM), diltiazem (70 microM), trifluoperazine (7 microM), cinnarizine (1.2 microM) and flunarizine (0.7 microM). Our results reveal that in rat brain synaptosomal fractions, calcium influx via the voltage-gated calcium channel appears to be more sensitive to diphenylpiperazine and phenothiazine groups; whereas, phenylalkylamine, benzothiazepine and dihydropyridine groups were relatively insensitive. This contrasts with the well known data obtained from vascular smooth muscle, in which the dihydropyridine group is the most sensitive of all the groups studied. Our results suggest that calcium channels in neuronal tissue are most likely different from those in non-neuronal tissue.