We have measured the concentrations of circulating oxytocin and the 13, 14-dihydro, 15-keto-metabolite of prostaglandin F2 alpha (PGFM) in women during preterm labor. Twelve women were given intravenous ethanol and 11 women received intravenous ritodrine for the prevention of preterm birth. Blood samples were obtained before and 1/2, 1, 2, 4, 12, and/or 24 hours after treatment began. On admission, the plasma concentrations of both oxytocin and PGFM were raised over levels observed in women with normal pregnancies of similar gestational age, 25 to 36 weeks. The initial oxytocin level was 58.5 +/- 8.2 pg/ml (mean +/- SE, n = 23) and the mean initial PGFM level was 264 +/ 33.1 pg/ml (n = 15); both values were significantly higher than in 10 control subjects (17.4 +/- 4.8 and 156 +/- 21.8 pg/ml, respectively). During infusion of ethanol, the plasma oxytocin level fell rapidly, the levels at 1/2 and 1 hour after infusion being significantly lower than before the infusion (29.0 +/- 5.5 and 27.8 +/- 3.5 pg/ml, respectively). The plasma oxytocin level remained low in women in whom the treatment arrested labor and prevented preterm birth (n = 8) but rose 2 to 4 hours after the infusion began in women in whom the treatment failed to arrest labor (n = 4). Ritodrine, on the other hand, had no significant effect on circulating oxytocin levels. The plasma PGFM level decreased significantly during ritodrine treatment only in the successfully treated patients. Ethanol had no consistent effect on plasma PGFM levels in the four patients in whom PGFM levels were measured. In the ritodrine-treated patients, the plasma PGFM level was positively correlated with the frequency of uterine contractions whereas in the ethanol-treated patients a correlation of plasma oxytocin to the frequency of contractions was observed. Thus, oxytocin secretion is increased during preterm labor, and the release of prostaglandin F is also increased. While it is not possible to determine whether any or both of these oxytocic agents actually trigger preterm labor, both seem to play a role in its mechanism.