Biopsy material from 24 adults with advanced stages of non-Hodgkin lymphomas (NHL) were examined for the distribution profiles of infiltrating cells following centrifugation to equilibrium on linear density gradients. Seven of these biopsies were predominantly composed of cells with high buoyant densities and 9 further biopsies predominantly of cells with intermediate buoyant densities. Both patterns were associated with favorable histologic features and with low proliferation of lymphoma cells. Intensive polychemotherapy was rarely required to achieve long-lasting disease control; in both groups, only 28% of patients died within a minimal observation period of 40 mo. In 8 biopsies, a predominance of light lymphoma cells was observed. This pattern was frequently associated with unfavorable histology and with high spontaneous tumor cell proliferation. Despite intensive polychemotherapy, rapid disease progression occurred in all cases, leading to death in 75% of the patients within a minimal observation period of 40 mo. Surface marker studies excluded the hypothesis that only the variable proportions of normal lymphocytes contaminating the lymphoma suspensions were responsible for the differences in the density distribution patterns described above; they rather suggested that these patterns reflect the individual capacity of a lymphoma to differentiate into dense tumor clones with low spontaneous proliferation.