Lymphocyte subpopulations were studied in the peripheral blood, lymph nodes, and spleens in a group of 17 patients with untreated Hodgkin's disease. In 12 of 15 cases, diminished absolute levels of T-lymphocytes in the peripheral blood were found; however, this was correlated with total lymphopenia. No direct relationship between "T-lymphopenia" and diminished cellular immunity, as measured by phytohemagglutinin and pokeweed mitogen blast transformation, and delayed cutaneous hypersensitivity was demonstrated. In eight lymph nodes involved histologically by Hodgkin's disease, a preponderance of T-lymphocytes was found when compared with a group of seven hyperplastic nodes (78.2 +/- 8.9% versus 54.5 +/- 11.0%, P is less than 0.01). These latter data appear to be consistent with the hypothesis that the pathogenesis of Hodgkin's disease involves a cell-mediated immune response to a neoplastic (antigenic) element.