To evaluate pituitary and pituitary-dependent target organ function in men infected with the human immunodeficiency virus (HIV), 26 ambulatory HIV-positive men (13 with acquired immunodeficiency syndrome [AIDS]) and nine healthy control men were administered rapid sequential injections of thyrotropin (TSH)-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), ovine corticotropin (ACTH)-releasing hormone (oCRH), and human growth hormone-(GH)-releasing hormone (hGHRH). Blood samples were collected before and for 90 minutes after the injections for immunoassay of pituitary hormones, cortisol, testosterone, and free thyroxine (fT(4)). Data were analyzed for each group of men considering basal, peak, and incremental responses to the releasing hormones, as well as the time course of response of each hormone. Mean basal serum GH concentrations were the same in all groups (control, AIDS, and non-AIDS HIV-positive), but stimulated GH levels were substantially higher at all time points in both groups of HIV-positive subjects. Results for prolactin (PRL) were similar, although stimulated PRL levels were increased significantly only in the AIDS group. The mean basal serum TSH concentration and stimulated TSH levels at 60 and 90 minutes were significantly greater in the AIDS group than in the control group. Basal mean fT(4) concentration in the AIDS group was significantly less than in the control group. Mean basal and stimulated serum (total) testosterone concentrations in all groups were the same. However, basal serum luteinizing hormone (LH) concentrations in both groups of HIV-infected men were significantly greater than in controls; stimulated (peak) LH levels were not different from control levels. Basal and peak stimulated plasma ACTH concentrations were significantly increased in both HIV-infected groups. Basal serum cortisol levels were also greater, on average, in HIV-infected groups, although stimulated (peak) cortisol responses were not different. These results indicate that basal serum concentrations of TSH, LH, ACTH, and cortisol are modestly increased in men with AIDS, and that maximum levels of GH, PRL, TSH, and ACTH stimulated by the releasing hormones are also increased in this group. Measurements obtained in the non-AIDS HIV-infected men showed a pattern generally similar to that obtained in men with AIDS, but less marked. The basis for the increased pituitary activity is unknown; we speculate that it is due to modestly impaired target organ function and to increased hypothalamic stimulation.