Interactions between the immune and endocrine systems may have an important role in ovarian tumorigenesis. Neonatal thymectomy at 3 days of age (Tx-3) in (C3H/HeMs x 129/J)F1 (C31) female mice results in an autoimmune ovarian dysgenesis then subsequent tumor formation. At 3 months of age the histology of the ovaries showed that approximately 60% of the Tx-3 mice (Tx-3 DO) had completely lost their oocytes and follicles so that a preponderance of interstitial-like cells remained. The remainder of the Tx-3 mice had atypical ovaries (Tx-3 AO). The vaginal cytology showed that both groups of Tx-3 mice became acyclic at an early age compared to the intact mice. Around 12 months of age, a high percentage of the dysgenic ovaries developed trabecular tumors. Plasma protein-related indicators of systemic inflammatory responses showed little change during the course of the autoimmune oophoritis or ovarian tumorigenesis. Levels of estradiol 17 beta (E2) and testosterone (T) did not vary in the Tx-3 mice compared to those of the intact mice through 21 months of age but progesterone levels were lower during the exacerbation of the autoimmune oophoritis and tumor development. By 24 months of age levels of P increased while E2 decreased. Apparently, the premature reproductive failure in these mice at a young-adult stage results from the early loss of the oocytes by the localized autoimmune insult to the ovaries. The autoimmune oophoritis may then be the primary trigger for the subsequent ovarian tumor formation and the tumors succeed in association with the altered hormonal milieu.