In this study we analyzed the expression of EB6 and GL183, which are part of P58 molecular family that represents the putative NK receptor for MHC class I molecules, in peripheral blood lymphocytes of 60 patients with HIV infection (20 asymptomatic HIV-seropositive individuals, 20 patients with constitutional symptoms, and 20 AIDS patients) and correlated it with the level of CD4(+), CD56(+) cells, and the NK cell activity in order to determine a possible relation with disease progression. The absolute number (but not the percentage) of CD56(+), EB6(+), and GL183(+) cells was significantly reduced only in AIDS patients but not in the other AIDS-related clinical conditions. On the contrary, NK cell activity was reduced in all HIV-infected patients. In a g-month follow-up, patients with constant clinical conditions and stable CD4(+) cells level showed no significant difference, either in the percentage or absolute number of EB6(+) and GL183(+) cells. Interestingly, dual-color fluorescence indicates that GL183 and EB6 molecules (that in normal individuals are virtually absent on CD3(-) NK cells) are expressed in HIV-infected individuals not only in CD56(+) cells but also in CD3(+) cells. This may reflect a depletion of other T cell subsets or alternatively (less likely) a specific immune response. Our data indicate that the expression of EB6 and GL183 in T and NK cells from HIV-infected patients might be relevant in the course of the disease and for the disease-associated functional defect of NK cell activity (C) 1994 Academic Press, Inc.