Immunophenotypic changes in peripheral blood mononuclear cells were analyzed by flow cytometry in several patient groups positive for cocaine in their urine. Single- and dual-color immunofluorescence staining was performed to examine total numbers of NK, T, and B cells, as well as the coexpression of surface molecules on T cells associated with memory function, helper/inducer capacity, and activation status. In addition, levels of several serum proteins (including immunoglobulins) and other demographic variables were evaluated. Our results show that cocaine-intoxicated patients display reductions in the total percentage of CD4+ T cells and increases in the number of NK cells. Dramatic shifts within certain T cell subpopulations were also observed. In particular, there appeared to be a preferential stimulation of "activated" T cells as indicated by increased levels of class II+ CD4 and CD8 T cells and IL2r+ CD4 T cells. "Memory" CD8+ T cell subpopulations (i.e., CD45RO+) were reduced in the cocaine-positive patients, whereas CD45R+/CD8+ T cells were accordingly increased in the same individuals. In some cases, direct correlation could be established between certain T cell percentages and cocaine levels. None of the serum protein levels measured appeared to be influenced by cocaine. These findings demonstrate that cocaine utilization is associated with variations in levels of certain T cell subpopulations and other immune cells. This may represent a disruption of particular immunologic cell networks which could ultimately influence host resistance to infection and malignancy.