The acute effects of intrastriatal kainic acid injection in nigrostriatal dopamine cell activity were assessed using electrophysiological and biochemical techniques. One hour after kainic acid injection, dopamine cell firing rates were significantly increased, as were striatal dopamine synthesis (dopa accumulation) and dopamine metabolism (3,4-dihydroxyphenylacetic acid levels). Twelve hours postkainic acid administration, cell firing rate had returned to control levels, as had dopa accumulation and DOPAC levels, but the number of dopamine cells firing had significantly decreased. Action potentials were elicited from the "silent" dopamine cells by iontophoretic application of gamma-aminobutyric acid but not glutamate. Conversely, 48 hr after kainic acid, the number of dopamine cells firing was significantly increased, as were 3,4-dihydroxyphenylacetic acid levels. Both cell firing rate and dopa accumulation, however, matched control values. The results are discussed in terms of the role of strionigral pathways in mediating the acute effects of kainic acid on the nigrostriatal dopaminergic system and are interpreted in light of the recently described phenomenon of presumed dopamine cell depolarization inactivation.