Rat substantia nigra slices were superfused with a physiological medium containing a diluted substance P (SP) antiserum, bacitracin and serum albumin to measure SP released in superfusates. As shown by measuring the degradation of a SP-labelled derivative incubated with cerebellar slices, this medium prevented the enzymatic inactivation of SP. Potassium (K+, 50 mM) and veratridine (5 X 10(-5) M) stimulated SP release and these effects were respectively prevented in absence of calcium and in presence of tetrodotoxin (5 X 10(-7) M). GABA (5 X 10(-5) M), nicotine (10(-6) M) and L-glutamic acid (5 X 10(-5) M) reduced the K+ (50 mM)-evoked release of SP. In contrast, glycine (5 X 10(-5) M), oxotremorine (5 X 10(-5) M), D-glutamic acid (5 X 10(-5) M) and serotonin (5 X 10(-5) M) were without effect. Pempidine (10(-5) M) prevented the inhibitory effect of nicotine (10(-6) M) on the K+-evoked release of SP. Glutamic acid diethyl ester (10(-4) M) completely abolished the L-glutamic acid-induced inhibition of the K+-evoked release of SP. Picrotoxin (5 X 10(-5) M) did not influence the L-glutamic acid inhibitory effect excluding the intervention of GABAergic mechanisms.