The amounts of protein synthesized and secreted (as indicated by [3H]leucine incorporation) by guinea-pig endometrium cultured for 24 h increased 2.1-fold between days 7 and 15 of the oestrous cycle. This increase did not occur if the guinea-pigs were pregnant. In ovariectomized guinea-pigs, oestradiol acting on a progesterone-primed uterus was the optimum stimulus for the maximum increase in endometrial protein synthesis and secretion. The two main proteins synthesized and secreted by day-15 guinea-pig endometrium had molecular masses of 99.8 and 192.1 kDa as determined on Sephacryl S-200HR. The production of the 99.8 kDa protein increased 5.2-fold between days 7 and 15 of the cycle. The 192.1 kDa protein was not detected in secretions produced by day 7 endometrium, and the 99.8 and 192.1 kDa proteins were not detected in secretions produced by day-15 pregnant endometrium. In ovariectomized guinea-pigs, progesterone did not stimulate the synthesis of secreted proteins of molecular masses above 77 kDa. Oestradiol stimulated the synthesis of secreted proteins with molecular masses of 87.8 and 192.1 kDa. However, oestradiol acting on a progesterone-primed uterus stimulated the synthesis of the secreted proteins with molecular masses of 99.8 and 192.1 kDa, which indicates that this combination of steroid hormones may be responsible for the increase in production of these two proteins by the day-15, nonpregnant guinea-pig endometrium. This stimulation by ovarian steroids of the synthesis and secretion of the 99.8 and 192.1 kDa proteins by the guinea-pig endometrium is apparently inhibited during early pregnancy.