Nine patients with premature ovarian failure, one of whom had the associated autoimmune disorders rheumatoid arthritis, Hashimoto's thyroiditis, and vitiligo, were examined for the presence of a serum factor which would interfere with gonadotropin-receptor interaction in a bovine testicular membrane system. Sera from nine premenopausal and nine postmenopausal women served as control subjects. Mean displacement of radiolabeled follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from receptors was not significantly different among the three groups. However, the greatest interference with FSH-receptor interaction was detected in the patient with both premature ovarian failure and autoimmune diseases. No differences in mean serum levels of IgG, IgM, and IgA were found among the premature ovarian failure and the two control groups, nor were immunoglobulin levels different in the otherwise unique subject (premature ovarian failure and autoimmunity). Our study suggests that anti-gonadotropin receptor factors are unlikely to be involved in the majority of patients with premature ovarian failure. However, an anti-FSH receptor factor, possibly an antibody, may be present in some patients, particularly those who have concomitant autoimmune disorders.