The NADase activity of the ectoenzyme CD38 on intact cells has been measured by a fluorometric assay using epsilon-NAD as a substrate. The enzyme activity was tested in the Daudi cell line, PHA-activated blasts and peripheral blood and tonsil lymphocytes from HIV-1-negative and -positive individuals. There was a direct correlation in all cells tested between the number of cell surface CD38 molecules added in the assay and the NADase activity of the same cells expressed as fluorescent units. This indicates that CD38 is expressed in its fully active form when up-regulated on T cells from HIV-1-infected patients. One of the suggested roles of the CD38 ectoenzyme is to degrade extra cellular NAD and thus recycle its permeable metabolites. This finding is consistent with the hypothesis that the increase in CD38 expression on lymphocytes during the chronic phase of HIV-1 infection is a mechanism to compensate for impaired capacity of these cells to synthesize ribonucleotides de novo.