The influence of nifedipine on the action of the antiepileptic drugs on the epileptogenic potential of the rat amygdala. The interaction of diazepam with fosphenytoin and nifedipine, as well as with their combinations, was studied in the amygdala-kindled rats. A combination of the lowest subconvulsive dose of diazepam with fosphenytoin was found to elicit a significant increase in the time to the second seizure of the amygdala kindled rats as compared to the sole treatment. Similarly, a similar combination of fosphenytoin and nifedipine (in equipotent doses) resulted in an elevation of the seizure threshold in the amygdala kindled rats. Thus, these results confirm our previous suggestion that besides its anticonvulsant effect, fosphenytoin exhibits a significant antiepileptogenic activity when used in combination with diazepam and nifedipine. The fact that no significant interactions were found between diazepam and nifedipine was shown by the lack of significant modifications in the response time to the second seizure. On the other hand, diazepam and fosphenytoin given in combination yielded a significant elevation of the seizure threshold. Thus, these data indicate the significant antiepileptogenic effect of fosphenytoin when used in combination with diazepam. The results of our study suggest that there might be a clinical benefit of using nifedipine and fosphenytoin in combination when combined therapy is required to control an epileptogenic focus.