The proliferation of lymphocytes from HIV-seronegative (HIV Ab-) and seropositive (HIV Ab+) individuals in response to two synthetic peptide epitopes of HIV envelope glycoproteins (ENVgp) was evaluated as an index of cell-mediated immunity in infected individuals. All HIV Ab- and most HIV Ab+ individuals' lymphocytes failed to proliferate in primary cultures in response to the two soluble HIV ENVgp peptides, ENVP346 and ENVP466 even in the presence of rIL-2. After stimulation with liposome-conjugates of ENVP346 or ENVP466 and soluble rIL-2, however, CD4 lymphocytes from some HIV Ab+ individuals were able to proliferate. Significantly higher frequencies of rIL-2-augmented proliferative responses to liposome-conjugated ENVP346 or ENVP466 were observed in HIV Ab+ asymptomatic individuals as compared to patients with AIDS-related conditions or AIDS. These studies indicate that the conjugation of HIV peptides or proteins to liposomes and stimulation with rIL-2 may enhance cell-mediated responses to these peptides.