The aim of this study was to investigate the ability of serotonin to increase contractions in human myometrium. Isometric tension measurements were used to determine the effect of increasing doses of serotonin on strips of human myometrium obtained at the time of cesarean section. Serotonin had little or no effect on the spontaneous activity of myometrium strips in control conditions. In tissue where this activity had been reduced by either forskolin or diazoxide, serotonin caused a dose-dependent increase in contractions and produced up to a 3-fold increase in contractions over basal activity. The ability of serotonin to increase contractions in the uterus appears to depend on the background activity of the tissue and is greatest in quiescent tissue. It is therefore possible that in quiescent, preterm myometrium, aberrant serotonin signaling could contribute to preterm labor. Serotonin may also play a key role in the postpartum prevention of uterine atony and consequent hemorrhage.