In high K+-depolarized spinal cord slices, capsaicin evoked the in vitro release of substance P and calcitonin gene-related peptide (CGRP) from central terminals of C-fibre afferents. This shows that capsaicin-induced release of neuropeptides from sensory afferents is not dependent on membrane potential changes, and that capsaicin-induced Ca2+-influx into nerve terminals does not require activation of voltage-sensitive calcium channels (VSCC). On the other hand, in the continuous presence of capsaicin, high K+ did not evoke release of CGRP, but only released substance P, which most likely originated from intrinsic substance P- containing neurones in the spinal cord. © 1990.