Objective: To evaluate the effect of natural progesterone on the relaxant effect of ritodrine on pregnant human oxytocin-induced myometrial contractility. Study design: 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. Results: 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). Conclusion: 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.