AbstractThe acute effect of intraperitoneal injection of phenytoin on rat peripheral nerve was studied. Conduction velocities in the ventral caudal nerve were measured hourly and phenytoin blood levels were obtained 4 to 5 hours after injection. Conduction velocity decreased by 23% in the 25 phenytoin‐treated animals from a control value of 30.0 ± 1.3 m/sec (mean ± SEM) to a 4‐hour value of 23.0 ± 1.3 m/sec (P<0.001). The phenytoin blood level 4 hours after injection was 45.0 ± 1.3 μg/ml. Amplitudes of evoked muscle action potentials in the treated group decreased by 37% from control values. High levels of phenytoin induce prompt slowing of nerve conduction velocity within hours, which may be mediated by mechanisms similar to those responsible for toxic central