The effects of neoplasia-induced hypercalcemia on the hypothalamic-pituitary axis of the Fischer rat were determined by measuring the responses of TSH to TRH, PRL to TRH and haloperidol, and LH to LHRH in 3 groups of 8 rats prior to and at 4 and 8 days after transplantation of a Leydig cell tumor. The mean serum calcium was 8.2 ± 0.2 mg/dl in 8 Fischer rats pretransplantation; had risen at 4 days posttransplantation to 9.8 ± 0.2 mg/dl; and at 8 days was 11.2 ± 0.1 mg/dl. TSH response to TRH was greater in the pretransplant rats than in the groups studied at 4 and 8 days posttransplant. Basal PRL levels and PRL responses to TRH and haloperidol were less in the groups studied at 4 and 8 days posttransplant. Basal LH values were similar in all 3 groups, but the LH response to LHRH was less for the posttransplant groups. The TSH response to TRH, PRL responses to TRH and haloperidol, and LH responses to LHRH were less in the 8 days posttransplants than in the groups studied at 4 days posttransplantation. There were significant negative correlations between TSH (r = -0.79) and PRL (r = -0.80) responses to TRH, PRL responses (r = -0.94) to haloperidol and LH responses (r = -0.91) to LHRH and the serum calcium. The results indicate that increasing levels of serum calcium following Leydig cell tumor transplantation are associated with suppression of adenohypophysial release of TSH, PRL, and LH; the degree of suppression is related to the magnitude of hypercalcemia achieved in this model.