In adult mice thymectomized at age 3 days (D3TX), increased incidences and/or levels of organ-specific antibodies to oocytes and/or zona pellucida, to testicular cell-sperm-differentiation antigens (TSDA), and to gastric parietal cells were detected, and these correlated significantly with oophoritis, orchitis (not epididymovasitis), and gastritis, respectively. The autoantibodies occurred in mice with the corresponding endogenous antigens. Thus, anti-oocyte/zona antibodies were detected in female, anti-TSDA antibodies in male, and anti-parietal cell antibodies in both sexes. Anti-oocyte/zona antibodies were first detected at age 5-6 weeks and were absent by 25 weeks. Serum antizona antibodies, but not anti-oocyte antibodies, inhibited mouse fertilization in vitro. In contrast, antibodies to sperm acrosome and antibodies to sperm surface did not correlate with testicular or epididymal disease. Moreover, both male and female mice had increased levels of anti-sperm surface antibodies, indicating that the sperm antigens detected may not be organ-specific. In addition, sera from 5-10% of D3TX mice reacted with a wide spectrum of epididymal and testicular antigens with defined cellular locations but of yet unknown specificity. Although the incidence of antibodies to cytoskeletal antigens was not significantly elevated after D3TX, anti-nuclear antibodies were more frequently detected in (SWR/JXA/J) F1 (SWRAF1) and (C57 BL/6J XA/J) F1 (B6AF1) mice after D3TX.