We report that fetal thymectomy inhibits oogenesis and induces abnormal ovarian differentiation in rhesus monkeys. In utero thymectomy (n = 5) elevated plasma follicle-stimulating hormone (7.8 +/- 1.1 microgram/ml vs. 4.2 +/- 0.5 microgram/ml; P less than 0.05) and decreased plasma prolactin (24.5 +/- 3.3 ng/ml vs. 76.3 +/- 11.2 ng/ml; P less than 0.05) concentrations compared with intact controls (n = 12), but did not change plasma luteinizing hormone, estradiol, cortisol, dehydroepiandrosterone sulfate, or thymosin-alpha 1 concentrations. In utero thymectomy reduced the weight of neonatal ovaries and adrenal glands, but not hepatic, renal, splenic, or total body weights. After fetal thymectomy, newborn ovaries (n = 8) contained a reduced total number of germ cells (123,926 +/- 11,651 vs. 432,034 +/- 40,311; P less than 0.001). The percentages of individual germ cell types were similar between thymectomized and intact groups (n = 11) except for an increased percentage of preantral-antral follicles in the thymectomy group (P less than 0.01). Our results indicate that the primate fetal thymus regulates antenatal ovarian follicular development, perhaps by interactions between the nascent immunologic and pituitary-ovarian systems.