To investigate prolactin (PRL) and thyrotropin-stimulating hormone (TSH) secretion in ovarian failure, 14 women with primary ovarian failure were challenged with luteinizing hormone-releasing hormone (LHRH) (100 micrograms) and thyrotropin-releasing hormone (TRH) (200 micrograms) given intravenously at 30-minute intervals. Responses were compared with those of 13 healthy female controls. In the patient group, basal follicle-stimulating hormone (FSH), LH, and peak gonadotropin responses to LHRH were higher and basal estrone and estradiol levels were lower than in the controls (P less than .001). Mean basal PRL levels were similar in the 2 groups. However, the mean peak and integrated PRL responses in the patients were greater than in the controls (P less than .05). Ten patients had a markedly exaggerated PRL response to TRH. The mean basal TSH levels and the peak TSH response to TRH were similar to those of the controls. Estrogens are known to stimulate PRL secretion. These subjects had increased PRL responses with low circulating estrogens. The mechanism underlying the findings is not known, but could be related to increased aromatization of androgens to estrogens in the hypothalamus. Alternatively, other factors could be responsible for the exaggerated PRL responses to TRH noted in these patients with primary ovarian failure.