To investigate the immune response of surgical patients to injury and sepsis, we measured total lymphocyte counts and T-cell subsets in five nonseptic and 17 septic subjects. Total lymphocyte and T-cell levels declined to similar degrees following injury or sepsis and did not appear to be of value as prognostic indicators. However, analysis of T-cell subsets in septic patients indicated that survivors exhibited normal T-cell subpopulations as well as helper to suppressor cell ratios. Nonsurvivors generally exhibited a selective depression of helper (OKT4) T-cells and the resultant degree of helper to suppressor ratio decline was directly related to mortality. A helper to suppressor ratio (OKT4/T8) below 0.6 was uniformly associated with a fatal outcome. Finally, a small subgroup of septic nonsurviving patients exhibited a selective depression of suppressor (OKT8) lymphocytes which also appeared to carry an unfavorable prognosis. These data indicate that T-lymphocyte subpopulation analysis is a useful predictor of hospital course.