We performed laparoscopic ovarian biopsies in 17 of 19 cases with premature ovarian failure. Primordial follicles were found in three cases, corpora albicanti in two, and epithelial-lined cysts in two cases. Chromosome analysis revealed a normal 46XX karyotype in 15 patients, 46XY in two, 45XO in one, and 46XO/46XX mosaicism in one patient. Immunofluorescence studies were performed on ovarian tissue obtained by laparoscopic biopsy in 12 cases with premature ovarian failure. Blood serum was analyzed for circulating anti-ovary and other autoantibodies in all 12 cases. Circulating autoantibodies were found in the serum of six patients, but not in healthy controls. Direct immunofluorescence was positive in 5 of 12 ovarian tissue samples with predominantly vascular wall staining. Indirect immunofluorescence was positive in 10 of 12 cases; antibodies reacting with ovarian stromal components were present in eight cases, antibody reacting with follicular epithelium was present in one case, and antibodies reacting with nuclear antigens were present in five cases. Two of the patients had anti-thyroid microsomal antibodies, and one had antitesticular antibody. We conclude that a significant number of patients with ovarian failure have serologic and biopsy findings suggestive of and consistent with autoimmunity, even though there are no overt clinical manifestations of autoimmune disease.