This study was undertaken to determine the characteristics of the proliferation of malignant and reactive cells in non-Hodgkin's lymphoma (NHL). Cell kinetics were studied in 76 previously untreated cases of NHL by flow cytometry after a double labeling of membrane antigen and DNA. Results were analyzed according to clinical and biologic characteristics of the patients. In B-cell NHL, percentages of B and T cells in S-phase were strongly linked (r = .82). The level of proliferation of malignant B cells and reactive T cells was significantly higher in aggressive lymphomas, compared with low grade, diffuse small cleaved cell NHL or reactive lymph nodes (P < .001). The percentages of malignant B cells in S-phase were lower when reactive T cells were more numerous (n = 59, r = -.264, P < .05), particularly in high-grade NHL (n = 16, r = -.78, P < .001). In the whole population of patients, survival was longer when the percentage of cells in S-phase (n1 = 38, n2 = 33) or S+G2 + mitosis (M) (n1 = 36, n2 = 35) was less than 3.2% and 7.25%, respectively (P < .005). When considering only B-cell NHL, survival was longer when the percentage of B cells in S-phase was less than 4.5% (n1 = 31, n2 = 28, P < .04). Among the slowly proliferative groups of lymphomas, this prognostic value was retained when S-phase value was less than 1% (n1 = 16, n2 = 13, P < .002). Furthermore, prognosis was better when the percentage of T cells in S-phase was less than 2.75% (n1 = 30, n2 = 29, P < .01) or when reactive CD4-positive T cells were more than 14.5% (n1 = 24, n2 = 24, P < .04). This result remained true in the group of highly proliferative lymphomas. These results illustrate the complexity of the interactions between malignant and reactive cells in NHL, with possible opposite effects on tumor cell growth.