Bath applied SP (2 x 10(-7) to 5 x 10(-7) M) produced a significant increase in the concentration of glutamate in the spinal slice perfusate, whereas the efflux of aspartate increased only with a higher concentration of SP (5 x 10(-6) M). The enhancement of the basal efflux of glutamate persisted in the absence of external Ca2+, but the effect was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP, a SP analogue claimed to be an antagonist of synthetic SP. Calcitonin gene-related peptide (CGRP 10(-7) M) produced a significant increase in the concentrations of glutamate and aspartate in the perfusate. Neonatal capsaicin treatment prevented the SP-induced increase in the release of glutamate. In contrast, the effect of CGRP was not significantly modified by the capsaicin treatment. These results indicate that SP and CGRP are capable of modulating the basal efflux of endogenous aspartate and glutamate and this modulation may represent one of the mechanisms by which these peptides contribute to primary afferent synaptic transmission.