Current research suggests that Ca2+ flux into the neuron may be a critical factor in the genesis of seizures. We report herein the influence of nimodipine, a selective central nervous system calcium channel blocker, in 60 rabbits with seizures that had been induced through ischemia, postischemia reperfusion, pentylenetetrazol, and bicuculline. In 30 animals subjected to 4 hours of ischemia, 9 of the 15 control animals had seizures in comparison with 1 of the 15 treated animals (P less than 0.005). Five animals with reperfusion seizures demonstrated similar results. In 10 animals in which a convulsant was applied topically to both cerebral hemispheres, unilateral intracarotid injection of nimodipine arrested seizures in that hemisphere alone, whereas the control contralateral hemisphere continued to have electrical seizure activity (P less than 0.001). Both placebo and verapamil were ineffective. These results suggest that Ca2+ influx is a common biochemical precipitant for various types of experimental seizures. Selective central nervous system calcium channel blockers may prove to be a new class of anticonvulsant agents.