OBJECTIVE To determine whether HLA-DR expression in the human ovary is controlled by endocrine or immune mediators, we examined the effects of several lectins, lymphokines, and hormones on granulosa cells in vitro. METHODS HLA-DR antigens were detected by indirect immunofluorescence on granulosa cells obtained at oocyte retrieval for in vitro fertilization. RESULTS When cultured with concanavalin A, pokeweed mitogen, phytohemagglutinin, interleukin-1, or interleukin-2, granulosa cells failed to express HLA-DR antigens. Both interferon alfa and interferon beta induced only a modest expression of HLA-DR molecules (4.1% +/- 0.9% and 2.5% +/- 0.8%, respectively) in comparison with the marked increase in HLA-DR expression (25.2% +/- 2.8%), when granulosa cells were exposed to interferon gamma. The gonadotropins follicle-stimulating hormone and human chorionic gonadotropin alone were unable to induce HLA-DR antigens, but acted synergistically with interferon gamma to enhance expression in a dose-dependent manner. The addition of 0.1 and 10 IU/ml of follicle-stimulating hormone with 10,000 IU/ml of interferon gamma significantly increased expression by 11.5% +/- 2.5% and 15.5% +/- 2.7%, respectively, over that of interferon gamma alone. Similarly, 1 and 10 IU/ml of human chorionic gonadotropin produced a 7.8% +/- 2.0% and 12.4% +/- 2.2% increase in HLA-DR expression over baseline. CONCLUSIONS These studies demonstrate that factors from both the immune and endocrine systems can interact to control HLA-DR expression in the ovary.