Oxytocin (OT) stimulates endometrial secretion of prostaglandin (PG) F2 alpha around the time of corpus luteum regression in ruminants, but the stimulus for luteolytic PGF2 alpha release in cyclic pigs is not clear. We previously reported that OT stimulates endometrial phosphoinositide hydrolysis and PGF2 alpha release in vitro, and that exogenous OT administered on Days 10-16 caused a uterine-dependent reduction in interestrous interval. In this study, the development of endometrial responsiveness to OT in cyclic, early pregnant, and ovarian-intact hysterectomized gilts was investigated. On Day 7 (onset of estrus = Day 0), 26 gilts were fitted with indwelling jugular catheters, and 5 of these gilts were hysterectomized. Cyclic (n = 5), pregnant (n = 6), and ovarian-intact hysterectomized (n = 5) gilts received i.v. injections of 20 USP units OT (equivalent to 20 IU or 40 micrograms/ml) on Days 10, 12, 14, and 16; and cyclic controls (n = 5) and pregnant controls (n = 5) received i.v. injections of vehicle. Concentration of 13,14-dihydro-15-keto-PGF2 alpha (PGFM; the major stable metabolite of PGF2 alpha) was measured in jugular venous plasma collected at 10-min intervals, from 20 min before to 120 min after i.v. injections of OT or vehicle. Plasma progesterone was measured in blood samples collected daily from Day 9 through return to estrus (cyclic gilts) or through Day 30 (pregnant and hysterectomized gilts). Vehicle-treated and OT-treated cyclic gilts were not responsive to OT on Days 10 and 12, and had similar plasma PGFM profiles on these days. However, OT-treated cyclic gilts were responsive (p < 0.01) to OT on Days 14 and 16, and peak concentrations of PGFM were detected in jugular plasma 10 min after OT injection. Concentrations of PGFM did not increase after vehicle injection on any day in controls. Similarly, PGFM in ovarian-intact hysterectomized gilts did not increase on any day after OT injection, indicating that the uterus was probably the source of OT-induced PGFM in cyclic gilts. Pregnant vehicle-treated gilts also did not have increased PGFM on any day after injection of vehicle. Pregnant OT-treated gilts had increased (p < 0.01) PGFM concentrations after OT injection on all days that were higher than concentrations in cyclic gilts on Days 10 and 12, but lower than those in cyclic gilts on Days 14 and 16 (p < 0.01). The concentration of plasma progesterone in cyclic gilts did not decrease until Days 15-16 (p < 0.01). Plasma progesterone was maintained in pregnant and hysterectomized gilts and was not influenced by OT treatment. These results indicated that 1) endometrial responsiveness to OT in cyclic gilts developed between Days 12 and 14 postestrus, 2) endometrial responsiveness to OT developed before luteolysis was initiated, and 3) endometrial responsiveness to OT in pregnant pigs developed before Day 10 of pregnancy and was attenuated on Days 14 through 16. These results are consistent with the hypothesis that OT may promote pulsatile luteolytic secretion of PGF2 alpha during corpus luteum regression in swine and that responsiveness to OT was suppressed to maintain corpus luteum function during early pregnancy.