The aims of this study were to investigate whether a nitric oxide (NO) system is present in the pregnant rat myometrium and whether it differentially inhibits myometrial contractility during midgestation and delivery at term. Myometrial strips were obtained from eight rats at midgestation (day 16) and eight rats during delivery at term, and mounted in an organ bath for assessment of isometric tension. There were scarce spontaneous contractions with gradually increased amplitude that ceased after short periods at midgestation, whereas the frequency of spontaneous contractions increased and were regular, and the amplitude of contractions became stable and long lasting during delivery. Spontaneous and carbachol-induced contractions were decreased by L-arginine and increased by N-G-nitro-L-arginine methyl ester (L-NAME) at midgestation and delivery, but much higher concentrations of L-arginine and L-NAME were required to obtain this effect at delivery. These results show: (1) that there is basal and carbachol-stimulated production of NO in pregnant rat myometrium; (2) that the L-arginine-NO system inhibits myometrial contractility; (3) that the effect of the L-arginine-NO system is elevated at midgestation and decreased during delivery; and (4) that the L-arginine-NO system may contribute to uterine quiescence during gestation and the initiation of labour at term. (C) 1998 The Italian Pharmacological Society.