Because T-regulatory cells (Tregs) can harmfully impair HIV-specific responses or beneficially limit immune activation, we compared the number of Tregs in lymph nodes from 48 HIV+ patients and 106 HIV- subjects. By using a microscope counting grid, we found that the mean ± SD number of Tregs in lymph nodes was 3 times greater in HIV+ males than HIV+ females (23.5 ± 20.7 vs 7.8 ± 7.7; P = .0006) and almost twice as great in HIV+ males than HIV- males (23.5 ± 20.7 vs 13.5 ± 15.5; P = .04). There were fewer Tregs in HIV+ females than in HIV- females (mean ± SD, 7.8 ± 7.7 vs 13.4 ± 13.3; P = .04). HIV+ males compared with HIV+ females had higher viral loads (VLs) and lower peripheral blood (PB) CD4 cell counts (mean ± SD, 239,841 ± 307,494 vs 73,038 ± 146,763 copies/mL and 262 ± 207 vs 466 ± 278/mm(3); P = .02 and P = .01, respectively). Our data show that Tregs in lymph nodes from HIV+ patients are positively correlated with VL and negatively correlated with PB CD4 counts. These findings suggest that Tregs might impair an HIV-specific immune response, which could be modified by sex, or, alternatively, an increased VL causes increased Tregs.