The existence of immunologic infertility is well grounded in the theories of humoral and cell-mediated immunology. Both of these immune system arms can theoretically and experimentally be shown to play roles in states of male factor infertility. Although much progress has been made in relating immunopathology to infertility, several problems plague the investigation and diagnosis: the use of multiple, different assay systems; the lack of properly controlled experimental work; a need to oversimplify a tremendously complex immunologic network for clinical purposes; and a dearth of communication between basic science and clinical investigators. Unlike the established role of humoral or antibody-mediated infertility, the way cell-mediated immunity induces reproductive failure is just beginning to be understood. Two active areas of investigation include a delineation of active immunosuppression in the normal testicular environment and the pathologic deficits induced by cytokines in cases of leukospermia. Other research seeks to define functional, sperm-specific antigens to which autoantibodies are directed and to elucidate the mechanisms of antibody-mediated infertility at various sites in the reproductive tract. The diagnosis of immunologic infertility still remains one of exclusion. When the diagnosis is made, it is necessary to define precisely which functional reproductive deficits exist, through an analysis of semen parameters, postcoital tests, sperm penetration assays, and tests of acrosomal reactivity. This is essential because the therapeutic options are broad and can involve significant side effects and expense. Proven modalities include sperm manipulation, direct sperm insemination, donor insemination, systemic immunosuppression, and assisted reproductive techniques.(ABSTRACT TRUNCATED AT 250 WORDS)