The membrane actions of calcitonin gene-related peptide (CGRP) and the effect on the Ca-dependent action potential of dorsal horn neurons have been investigated by means of an intracellular recording technique in the immature rat in vitro spinal cord slice-dorsal root ganglion preparation. Bath application of CGRP (10(-8)-10(-6) M for 1-10 min) produced a slow reversible depolarization in about one-third of the cells examined. Biphasic membrane response consisting of an initial hyperpolarization followed by a late prolonged depolarization was seen in a smaller proportion of tested cells. Both membrane responses were present, and even enhanced, when synaptic transmission and Na spikes were blocked by perfusing the slice with a TTX-containing Krebs solution. The CGRP-induced membrane changes were also present in media containing TTX and TEA. The CGRP-evoked depolarization was associated with an increase in the input resistance, and enhanced excitability in a majority of neurons tested. In addition, CGRP modified the duration of Ca-dependent action potentials of dorsal horn neurons, the most consistent change being a prolonged increase in the spike duration. Our results are consistent with a neurotransmitter or neuromodulator role for CGRP in the rat spinal dorsal horn.