The effects of gamma-vinyl-GABA (4-amino-hex-5-enoic acid, RMI 71754) and gamma-acetylenic-GABA (4-amino-hex-5-ynoic acid, RMI 71645), the selective and irreversible inhibitors of GABA-transaminase (E.C. 2.6.1.19), on the resting and stimulated release of GABA and other amino acids from sensorimotor cortex of rats was studied using a superfusion technique. Administration of a single dose of gamma-vinyl-GABA (1500 mg/kg i.p.) caused the appearance of GABA in superfusate. This reached a maximal peak size after 50 min and remained high for 3 h. gamma-Vinyl-GABA was also released and reached a maximum value after 20 min and decreased to low levels during 3 h. There was no direct parallelism between the time courses of release of GABA and gamma-vinyl-GABA. Also, the amount of GABA released was much larger when the drug was administered by i.p. injection than when applied directly to the cortex surface through the cannula at 100 microM. In the presence of gamma-vinyl-GABA, stimulation of the brachial plexus contralateral to the superfusion cannula increased GABA and glutamate release, but was without effect on gamma-vinyl-GABA itself or any other amino acid. In the presence of gamma-acetylenic-GABA the contralateral stimulation increased significantly only the rate of release of glutamate and the combined peaks of GABA and gamma-acetylenic-GABA. These changes were not observed to follow stimulation of the ipsilateral plexus. Stimulation of either plexus had no detectable action on the rates of release of GABA from the visual cortex. The changes in rates of release of GABA and glutamate due to stimuli were reversible, returning to control levels after cessation of the stimulation.