With hippocampal slice electrophysiology, direct evidence that mineralocorticoid receptors (MR) mediate excitatory effects of corticosteroids on neuronal activity was found. The present experiments extended this hypothesis to a whole animal model. The effects of manipulations of MR binding on convulsions produced by pentylenetetrazol (PTZ), strychnine and kainic acid were examined. Moderate increases in plasma corticosterone levels resulted in enhanced susceptibility to several convulsion types; decreased levels attenuated the susceptibility. The proconvulsant effects of corticosterone were inhibited by the MR antagonist, spironolactone. Convulsions typically affected by these manipulations were PTZ-induced myoclonic jerk and face and forelimb clonus and kainic acid-induced convulsions. Other convulsion types, e.g., PTZ-induced running bouncing clonus and tonic hindlimb extension and strychnine-induced convulsions, were generally unaffected by these manipulations, which suggests that central MR effects are not global. The convulsions that were sensitive to MR manipulations are believed to originate in limbic structures. These results provide the first direct evidence for a role of central MRs in the modulation of central nervous system excitability in a whole animal. Furthermore, they suggest that central MR action may be important in disruptions of excitability, such as epilepsy, drug withdrawal syndromes and arousal states in healthy animals.