A high incidence of autoimmune oophoritis can be induced in (C57BL/6Cr x A/J)F1 mice that were thymectomized at 3 days of age. The vaginal opening day was significantly delayed (thymectomized mice [n = 35], 38.1 +/- 5.8 days [mean +/- SD] versus sham thymectomized mice [n = 26], 34.0 +/- 5.2 days; p less than 0.02). Most of the thymectomized mice showed irregular estrous cycles during the first several weeks and then fell into continuous diestrus. Local infiltration of mononuclear and plasma cells inside and around growing follicles was a prominent feature in the early stage of oophoritis. This abnormal feature was first noticed at 24 days of age and progressed in the follicular units. Acute loss of oocytes, especially of growing follicles, with massive mononuclear cell infiltration rapidly progressed after puberty, and atrophic ovaries with complete destruction of both primordial and growing follicles were then seen for 1 to 2 months after puberty. In mice with oophoritis, circulating autoantibodies against, ooplasm, zona pellucida, or steroid-producing cells were constantly detected by immunohistochemical assay. Autoimmune thyroiditis and gastritis accompanied by specific circulating antibodies were also detected in mice thymectomized at 3 days of age. This experimental model may serve as a tool for studying premature ovarian failure in humans.