The possible mode of action of an inhibitory neuropeptide SchistoFLRFamide (PDVDHVFLRFamide) on locust oviduct visceral muscle was studied by examining its ability to inhibit calcium ionophore A23187-, caffeine- or phorbol ester-induced oviduct contractions. A23187-induced muscle contractions included two components: one which required the influx of extracellular Ca2+ through Ca2+ channels (blocked by cobalt ions), the other not blocked by cobalt ions. SchistoFLRFamide inhibited the cobalt-sensitive components, but not the latter. Caffeine induced two phases of contractions, a phasic contraction which was probably due to the release of intracellular Ca2+ and a tonic contraction which required the influx of extracellular Ca2+. SchistoFLRFamide inhibited the tonic contraction in a dose-dependent manner but did not influence the phasic contraction. The phorbol 12-myristate 13-acetate-induced muscle contraction required the presence of extracellular Ca2+, with Ca2+ probably entering through ligand-gated channels, but the contraction was not inhibited by SchistoFLRFamide. Based upon these results, it appears that SchistoFLRFamide inhibits muscle contraction by preventing the accumulation of free intracellular Ca2+ from extracellular stores. SchistoFLRFamide is incapable of inhibiting contraction induced by the release of intracellular stores of Ca2+. It is possible that SchistoFLRFamide closes or blocks voltage-gated and some ligand-gated Ca2+ channels in the plasma membrane.