- The frequency-dependent effect of various anticonvulsant drugs on the conduction in central axons was studied in the corpus callosum of rat and guinea pig brain slices from the parietal region. Extracellularly recorded compound action potentials (CAPs) were evoked by either single stimulus or high frequency stimulation (40–80 Hz). The CAP in rats consisted of an early component (fast axons, 1.2–1.8 m/s) and a late component (slow axons, 0.5–0.7 m/s), while in the guinea pig only the slow phase was observed. Diphenylhdantoin increased the latency of a single response by 10%, and had no effect on the CAP amplitude. In contrast, both phenobarbital and pentobarbital reduced the amplitude of singly evoked CAPs. Stimulation at high frequency alone decreased the CAP amplitude by 10–20%. Identical stimulation in the presence of the drugs further suppressed the CAP amplitude by an additional 31%, with varying degree of drug efficacy. The depressant effect was significant for the slow axons but the fast axons were virtually unaffected by any of the drugs. The results are consistent with the hypothesis that the antiepileptic drugs DPH, Phe and Pnt may block axonal conduction from an epileptic focus into neighbouring areas of the brain.