Peripheral blood lymphocyte cell surface markers were studied in 146 patients with various forms of acute infection using B cell identification with antisurface immunoglobulin and T cell subset enumeration with hybridoma T cell subpopulation reagents. Significant depression was recorded in total numbers of T cells and T cell helper-inducer and suppressor-cytotoxic subsets in pneumonia, acute pyelonephritis, and severe generalized sepsis. In addition, proportions of T cells being the OKT4 helper-inducer phenotype were reduced only in patients over the age of 60 with pneumonia or sepsis. Patients with severe infection frequently had multiple T cell phenotypic surface marker abnormalities. In some instances, when depressions of total T cell numbers as well as respective helper-inducer or suppressor-cytotoxic T cells were noted in the face of generalized sepsis, lack of improvement in these abnormalities during the course of treatment was associated with rapid clinical deterioration and death. On the contrary, in patients with a successful response to appropriate therapy, initial depressions of total T cell numbers and subsets improved progressively with clinical resolution of sepsis and illness.