To evaluate the effect of natural progesterone on the relaxant effect of ritodrine on pregnant human oxytocin-induced myometrial contractility.Isometric tension recordings were performed under physiologic conditions on isolated myometrial strips taken from low-risk term pregnant women undergoing elective cesarean section. Cumulative effects of natural progesterone (10 −11 to 10 −5 mol/L) on oxytocin-induced myometrial contractility were evaluated. Contractile activity following ritodrine exposure was also investigated in myometrium pretreated with natural progesterone.Natural progesterone alone exerted a concentration-dependent relaxant effect on myometrial contractions. The concentration-response curve for ritodrine from natural progesterone pretreated myometrium was shifted to the left with a significant reduction (P < .01) of 50% of the maximal response, contraction amplitude (P < .05), and frequency (P < .05). However, there was no significant difference in the mean maximal inhibition achieved (P=.95).Natural progesterone increased the relaxant effect of ritodrine by reducing 50% of the maximal response, amplitude, and frequency of myometrial contraction, most likely through nongenomic actions.These results suggest that natural progesterone may be beneficial for preventing preterm birth in a low-risk population.