Inhibiting human immunodeficiency virus (HIV) replication with potent antiretroviral therapy may result in improved immune function, and this may lead to favorable outcomes, independent of changes in CD4(+) lymphocyte count, The effect of combination protease inhibitor therapy (ritonavir plus saquinavir) on functional measures of cell-mediated immunity in 41 HIV-infected patients from one center of a multicenter trial was investigated, After 24 weeks, median plasma virus load decreased from 4.74 log(10) copies/ml to below the detection limit of the assay (2.30 log(10)), and mean CD4(+) lymphocyte count increased from 284 cells/mu L to 413 cells/mu L, Proliferative responses to phytohemagglutinin developed in 21 of 34 patients in whom responses were absent at baseline. Increases were observed in interleukin-2, -12, and -10 production and in the expression of CD28 on CD8(+) lymphocytes, Initiation of potent anti-HIV therapy results in a degree of immune restoration, suggesting that HIV-induced immune suppression is a dynamic and potentially reversible process.