In this study we analyzed the behavior of a CD3(+) T cell subpopulation lacking CD5 antigen expression in PBMC from HIV-1-infected patients. CD3(+)CD5(-) lymphocytes were greatly increased in peripheral blood of HIV-1(+) patients, accounting for 20.6 +/- 9.9% of the total CD3(+) cells, compared to seronegative individuals (5.5 +/- 3.2%). In both seropositive patients and controls, CD3(+)CD5(-) cells belonged to the CD8(+) compartment; they were nonactivated, TCR alpha/beta(+), naive lymphocytes, and in seronegative individuals preferentially expressed NK cell-associated markers, such as CD11b, CD16, CD56, and CD57. The phenotypic profile of this subset was slightly different in seropositive patients; while TCR expression and CD45RA/RO profile were comparable, CD11b and CD16 expression was lower compared to control figures, while CD56 expression was not changed, and CD57 expression was enhanced. Functional analysis of enriched CD3(+)CD8(+)CD5(-) cells showed an impaired ability to proliferate in response to mitogenic and antigenic stimuli; despite their NK-like phenotype, CD3(+)CD8(+)CD5(-) cells did not exert any NK cytotoxic activity, and only a lectin-dependent cytotoxic potential could be evidenced in this population. These results describe a novel alteration in the lymphocyte phenotypic profile during HIV-1 infection, involving a ''transitional'' population, which shares some properties of the T and of the NK cell lineage. (C) 1995 Academic Press, Inc.