Caruncules are differentiated sites of the endometrium in which placentation occurs in ruminants. We investigated whether the response to agents involved at the time of recognition of pregnancy differed in the caruncular (CAR) and inter-caruncular (ICAR) areas of the endometrium in vitro. The specialization in prostaglandin (PG) production previously described in cells from whole endometrium was reproduced in the CAR and ICAR areas: PGF(2 alpha) and PGE(2) were produced in greater proportions, respectively, in epithelial and stromal cells. The relative production of PGE(2) was equivalent in epithelial cells from CAR and ICAR regions, but the production of PGF(2 alpha) was higher (p < 0.05) in the ICAR region (2.2 +/- 0.5 vs. 4.0 +/- 0.2 ng/mu g DNA, respectively). In stromal cells, the ICAR area produced more PGE(2) than did the CAR area (3.4 +/- 0.4 vs. 2.1 +/- 0.4 ng/mu g DNA, p < 0.05), and the respective PGE(2):PGF(2 alpha) ratio was significantly higher in the ICAR area (p < 0.05). The production of PCs was measured first in response to oxytocin (OT, 10(-9) to 10(-5) M) and then to recombinant ovine interferon-tau (roIFN-tau, 0.02 to 20 mu g/ml) in a separate set of experiments. In epithelial cells, OT stimulated the production of PGF(2 alpha) 6.3-fold in the CAR area and more than 33.0-fold in the ICAR area (7.1 +/- 3.2 vs. 36.3 +/- 9.8 ng/mu g DNA, respectively, p < 0.05). Production of PGE, was also increased in both regions and reached a plateau at 4.1 +/- 0.4 ng/mu g DNA. In epithelial cells from the ICAR but not the CAR region, the PGE(2):PGF(2 alpha) ratio was decreased in the presence of OT (p < 0.05). In separate experiments, addition of roIFN-tau stimulated PGE, production significantly (p < 0.05), and no difference (p > 0.8) was observed between CAR and ICAR regions. An increase in PGE(2):PGF(2 alpha) ratio was observed in epithelial cells from both CAR and ICAR regions, but it was significant only in the CAR region (p < 0.05). In stromal cells, roIFN-tau stimulated PGE(2) production significantly in cells from the CAR and ICAR regions (35.6 +/- 2.9 vs. 24.1 +/- 3.8 ng/mu g DNA, respectively, p < 0.05). In summary, the ICAR region seems to be the privileged site for regulation of PGF(2 alpha) production by OT, but the caruncules may be a preferred site for recognition of the embryonic IFN-tau signal. Endometrial cells from the CAR and ICAR areas appear to exhibit specialized responses, with cells from the ICAR region more responsive to OT and those from the CAR region more sensitive to roIFN-tau.