In order to differentiate between a prolactin-secreting adenoma and a nonneoplastic etiology for galactorrhea, a single stimulatory dose of 500 microgram of thyrotropin-releasing hormone (TRH) was employed to assess the prolactin (PRL) response of 50 women. The results were compared to those obtained in 19 control subjects (10 with subsequent surgical removal of a PRL-secreting those obtained in 19 control subjects (10 with subsequent surgical removal of a PRL-secreting adeonoma and nine women stimulated in the early follicular phase). All patients were grouped according to normal or elevated serum PRL, and normal, equivocal, or abnormal findings by tomography of the sella turcica. Patients with a normal baseline PRL had a normal PRL response to TRH of at least 200% above baseline. This normal response was independent of findings by tomography of the sella turcica. A highly significant difference in response (p < 0.001) was illustrated by all patients with elevated PRL and abnormal tomograms, and in some patients with elevated PRL and normal or equivocal tomograms. These responses were identical to those of the control patients who had histologic evidence of a PRL-secreting adenoma. The findings indicate that a PRL-secreting adenoma in patients with galactorrhea can be identified on the basis of the PRL response to TRH stimulation.