Gonadotropin responses to GnRH and PRL responses to TRH and metoclopramide (MTC) were investigated in nine consecutive women with amenorrhea and insulin-treated diabetes mellitus. Nine normal menstruating diabetic women, 12 normal women in the early follicular phase, and nine consecutive nondiabetic women with functional amenorrhea served as controls. No significant differences were found in relation to diabetes regulation within the two diabetic groups. Amenorrheic patients with diabetes mellitus had significantly lower basal PRL levels than normal women and estradiol levels compared to the other groups. Basal plasma LH concentrations were significantly lower in women with amenorrhea and diabetes mellitus than in nondiabetics with amenorrhea, whereas plasma FSH levels were similar in all groups. The LH response to GnRH was significantly lower in amenorrheic patients with diabetes mellitus than in normal women, and a significant correlation (r = 0.81, P less than 0.01) was found between the LH response to GnRH and the basal estradiol level in these women. The FSH response to GnRH and the PRL response to TRH were similar in all groups. Amenorrheic diabetics had significantly lower PRL responses to MTC compared to other groups, and nondiabetics with amenorrhea had significantly lower PRL response than normal women. It is concluded that diabetic patients with functional amenorrhea have low basal and MTC-stimulated PRL levels, low basal LH levels, and decreased LH response to GnRH despite low estrogen levels. These hormonal changes may in part be caused by a raised central dopaminergic activity leading to a depression of pituitary ovulatory mechanisms.