Cyclic AMP levels and glycogen phosphorylase a activity were investigated in the cerebral cortex of mice during seizures induced by 3-mercaptopropionic acid (MP). The onset of seizure was associated with a 3-fold increase of cyclic adenosine 3′,5′-monophosphate (c-AMP) and rapid activation of glycogen phosphorylase a (60% in the a form, i.e. to about double the values of the controls). Five minutes after the end of convulsions, both the levels of cyclic AMP and phosphorylase a activity were already restored to control values and remained unchanged during the subsequent 5 min. Sodium phenobarbital not only prevented clinical manifestations of MP convulsions, but also the changes in cyclic AMP content and phosphorylase activation observed during convulsions. These findings support the suggestion that cyclic AMP participates in the regulation of glycogen metabolism in the brain similarly as in other organs. The rise of cyclic AMP accompanying MP seizures was not influenced by the pretreatment of mice with theophylline which suggests that adenosine is probably not involved as a mediator of enhanced levels of cyclic AMP. The accumulation of cyclic AMP during MP seizures was markedly reduced by dl-propranolol (by about 20% and 80%, respectively, depending on the dose of propranolol used). This suggests that during MP seizures the possible release of endegenous catecholamines might interact with cyclic AMP generating system. Propranolol failed, however, to influence the activation of phosphorylase a. The failure of propranolol to protect activation of phosphorylase may be due to the fact that either a small increase in c-AMP (remaining after propranolol pretreatment, +20%) is sufficient for maximal activation of the enzyme or that other factors (e.g. Ca 2+) participate.