Effect of acetazolamide (AZA) on the anticonvulsant potency of several antiepileptics was investigated in mice by maximal electroshock seizure test. By the coadministration of AZA, a remarkable increase in the anticonvulsant activity was brought about not only for the barbiturates including barbital (BA), mephobarbital (MB) and metharbital (MET), but also for the other antiepileptics such as phenytoin (PHT), valproic acid (VPA) and trimethadione (TMO). This potentiating effect of AZA, however, was relatively weak for PHT, MET and TMO (about 2.5 fold) in contrast to those for phenobarbital (PHB), BA, MB and VPA (4-5 fold). The brain-serum concentration ratio (B/S) of PHB was elevated by the coadministration of AZA, while the B/S of PHT was not changed. Thus it was inferred that the difference in the potentiating effect of AZA on the activity of the antiepileptics was due to the difference in its effect on the brain levels of the antiepileptic drugs. However, the potentiating effect of AZA was still observed for PHT, VPA and MET, as well as PHB, in reserpinized mice. Therefore, some pharmacodynamic effect of AZA other than its increasing effect on the brain levels of the antiepileptic drugs may partly contribute to the potentiation of the activity of the antiepileptic drugs.