Immune function changes during pregnancy and human immunodeficiency virus (HIV) infection. T helper function and phenotypes in HIV-infected and -uninfected pregnant and postpartum women and nonpregnant uninfected control women were studied. T helper function was assessed by interleukin-2 (IL-2) production in vitro and three-color flow cytometry. All uninfected nonpregnant subjects, 74% of uninfected pregnant subjects, and only 54% of HIV-infected pregnant subjects responded to all stimuli. All uninfected subjects 2-6 months postpartum had normal function versus 27% of infected subjects (trend P < .001). Uninfected pregnant subjects had reduced levels of CD4+CD45RA-RO+ (memory) and elevated levels of CD4+CD45RA+RO- (naive) lymphocytes. Infected pregnant subjects had elevated levels of memory, reduced levels of naive, and increased levels of CD4+HLA-DR+CD38+ (activated) lymphocytes. Increased CD4+DR+CD38+ cells correlated best with poor IL-2 function, HIV infection, and being postpartum (R2 = .79). Thus, T helper function and phenotypes are altered in pregnancy and return to baseline postpartum in uninfected but not HIV-infected women.