Colleagues-Although adrenal gland morphologic abnormalities have often been observed in autopsy series ofpatients with AIDS, clinically significant adrenal insufficiency has been infrequent in patients living with human immunodeficiency virus type 1 (HIV-l) infection [1]. In a recent report, Villette et al.[2] demonstrated that HIV-l-infected adult patients have alterations of adrenocortical circadian rhythms, elevated morning plasma cortisol levels, and elevated 24-h adjusted mean plasma cortisol levels compared with HIV-I-seronegative controls. We prospectively studied HIV-L-infected patients at various clinical stages to study the effect of HIV-1 infection on the circadian rhythms ofserum cortisol levels and CD4+ lymphocyte counts. The CD4+ lymphocyte count data from this study were previously published [3], documenting circadian rhythms of CD4+ lymphocyte counts that could contribute to the observed variability ofrepeated CD4+ lymphocyte counts in HIV-I-infected patients. These CD4+ lymphocyte fluctuations were much smaller in magnitude than the large-amplitude, evening-peaking CD4+ cycle observed in HIV-I-seronegative controls. Sixteen HIV-infected adult male military patients classified with the Walter Reed (WR)[4] staging criteria (7 in WR 1-2, 5 in WR 3-5, 4 in WR 6 [AIDS]), and 6 HIV-L-seronegative ageand sex-matched controls were prospectively and repeatedly phlebotomized over the course of the day to study causes of variability of CD4+ helper lymphocyte counts and serum cortisol levels. Blood specimens were drawn at 8: 00 AM and 10: 00 PM from all patients on the first day of the study for serum cortisol and CD4+ lymphocyte counts. Blood for CD4+ lymphocyte counts was also drawn at noon and 4: 00 PM on the first day and at 8: 00 AM, noon, and 4: 00 PM for 2 additional consecutive days and then processed as previously described [3]. Serum cortisol levels were measured during a single batch run from previously frozen specimens using a radioimmunoassay kit (Clinical Assays, GammaCoat Cortisol; Baxter Healthcare, Cambridge, MA). Patients were not prescribed or known to be taking any medications that could have confounded the interpretation of serum cortisol levels or lymphocyte counts. The observed serum cortisol levels (# lg/dl) and CD4+ lymphocyte counts (cells/rnrrr') at 8: 00 AM and 10: 00 PM are presented in table 1. The HIV-infected patients (at all clinical stages) showed increased morning cortisol levels compared with those of the HIV-I-seronegative controls, with statistically significant differences from the WR 6 group (P<. 03, Mann-Whit-