The depolarization-evoked release of gamma-aminobutyric acid (GABA) and its possible modulation mediated by autoreceptors were studied in nerve endings isolated from rat spinal cord and prelabeled with the radioactive aminoacid. In the presence of the GABA uptake inhibitor SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid], used to minimize carrier-mediated homoexchange, exogenous GABA (1-10 mumol/l) decreased in a concentration-dependent way the release of 3H-GABA evoked by 15 mmol/l KCl. The GABAA receptor agonist muscimol (10-100 mumol/l) did not affect the K+ (15 mmol/l)-evoked 3H-GABA release. Similarly ineffective was the GABAB receptor agonist (-)-baclofen (3-100 mumol/l). The effect of GABA was not counteracted by the GABAA receptor antagonists bicuculline,picrotoxin or SR95531 [2-(3'-carbethoxy-2'-propenyl)-3-amino-6-paramethoxy-phenyl-pyr idazinium bromide].(ABSTRACT TRUNCATED AT 250 WORDS)