Oxytocin stimulates secretion of endometrial prostaglandin (PG) F2 alpha and induces endometrial phosphoinositide hydrolysis around the time of regression of the corpus luteum (CL) in cows. This study investigated the relationship between endometrial oxytocin receptors, oxytocin-stimulated phosphoinositide hydrolysis and PGF 2 alpha secretion in vitro, and plasma concentrations of ovarian steroids before and during CL regression in cyclic heifers (i.e., Days 13-19 post-estrus). Reproductive tracts were collected from 16 cyclic heifers on Days 13 (n = 5), 16 (n = 5), and 19 (n = 6). Decreases in mean CL weight (4.7, 4.6, and 3.0 +/- 0.6 g for Days 13, 16, and 19, respectively; p< 0.05) and plasma progesterone (12.2, 10.5, and 4.3 +/- 1.5 ng/ml for Days 13, 16, and 19, respectively; p < 0.01) were detected between Days 16 and 19, indicating that CL regression had been initiated in the group of Day 19 heifers. Mean concentration of plasma estradiol (3.4, 3.8, and 5.6 +/- 1.7 pg/ml for Days 13, 16, and 19, respectively) did not differ significantly (p > 0.5) among days of the estrous cycle. Concentration of endometrial oxytocin receptors increased (p < 0.06) during the estrous cycle (36, 49, and 789 +/- 234 fmol/mg protein on Days 13, 16, and 19, respectively), but the greatest increase (p < 0.05) occurred between Days 16 and 19. Similarly, incorporation of [3H]inositol into endometrial inositol phosphates induced in vitro with 100 nM oxytocin also increased (p < 0.01) during the estrous cycle (5121 vs. 5819, 4529 vs. 7239, and 5888 vs 68,096 +/- 18,564 dpm/g tissue for control vs. oxytocin-treated endometrium on Days 13, 16, and 19, respectively) with the greatest increase (p < 0.01) in responsiveness to oxytocin occurring between Days 16 and 19.(ABSTRACT TRUNCATED AT 250 WORDS)