We retrospectively evaluated correlates of increases in CD4 cell count in antiretroviral agent-naive subjects with fewer than 50 copies per milliliter of plasma human immunodeficiency virus ribonucleic acid who were participating in a study of indinavir, lamivudine, and zidovudine therapy. Pharmacologic data from intensive pharmacokinetic studies and baseline patient characteristics were evaluated as predictors of the increase in CD4 count from baseline to weeks 24, 56, and 80. Relations were investigated with regression analysis. Of all covariates, maximum plasma concentration (Cmax) of indinavir was significantly and uniquely associated with increases in CD4 count from baseline to all end points (P = .002 at week 80; n = 20). At week 80, subjects with a Cmax greater than the overall group median value of 7 μg/ml had an increase in CD4 count of 358 cells/μl versus 197 cells/μl for those with a Cmax less than 7 μg/ml (P = .006). These data suggest distinct pharmacodynamic relations exist for immune reconstitution and suppression of plasma human immunodeficiency virus ribonucleic acid. We hypothesize this new finding may be associated with expression of P-glycoprotein.