We examined the effects of substance P, [D-Arg1, D-Trp7, 9, Leu1 1] substance P (spantide) and lidocaine on the compound action potentials (APcs) of the rat sciatic nerve in vitro. Substance P had no effect but spantide suppressed the APcs of both A- and C-fibers in a dose-dependent manner and this suppression was reversible at 10(-4) M but irreversible at 10(-3) M. Lidocaine also suppressed the APcs reversibly but spantide was more potent than lidocaine. There seemed to be differences in the suppressing mechanism between the two drugs.