To examine the responsiveness of prolactin (PRL) secretion in patients with PRL-producing tumor (PRL-noma), TRH (500 micrograms), arginine (0.5 g/kg, b. wt.), and sulpiride (100 mg) were administered to 13 patients with PRL-noma. Seven of these patients responded to TRH or other agents with an increase in their plasma PRL levels of 50% or more above the basal values (categorized as Group I). The remaining six patients, however, showed no response to any of these agents (categorized as Group II). After the administration of L-dopa (500 mg, p.o.), Group I patients showed significantly greater decreases in plasma PRL (-68.9 +/- 6.6%) from the basal value than did Group II (-37.4 +/- 8.6%; p less than 0.02). The mean basal PRL levels were higher in Group II than in Group I, although these differences failed to reach statistical significance. Moreover, there were no differences in age, sellar volume, or the presence of bitemporal hemianopsia between the two groups of patients. It is concluded that there are two patterns of PRL-secretory responses to pharmacological stimuli in patients with PRL-noma. The differences between the two patterns might be characterized by the properties of the lactotroph cells themselves rather than by the relation of these cells to the hypothalamus.