Eighty previously untreated patients with B-cell chronic lymphocytic leukemia (B-CLL) were analyzed to study the proliferation rate of their peripheral blood (PB) leukocytes to determine its relationship with the extension of the disease and its value in discriminating among patients with similar tumor cell mass. The 80 B-CLL patients were distributed into two different groups according to the absolute count of PB S-phase leukocytes: a low proliferative group (less than 1 x 10(9)/I) of 48 patients and a high proliferative group (greater than or equal to 1 x 10(9)/I) of 32 patients. The high proliferative group displayed a higher incidence of splenomegaly (p less than 0.005), hepatomegaly (p less than 0.08), anemia (p less than 0.02) and thrombocytopenia (p less than 0.03) as well as a higher lymphocytic infiltration both in PB (p less than 0.0004) and in bone marrow (BM) (p less than 0.003). These patients also showed a higher incidence of a diffuse pattern of BM involvement (p less than 0.04), advanced clinical stages [stage III/IV (p less than 0.03) and group C (p less than 0.04)] and infections (p less than 0.0008) together with significantly lower IgG (p less than 0.03) and IgM (p less than 0.03) serum levels. Regarding the immunophenotype, there was a greater percentage of either CD19+ (p less than 0.06) and CD19+ CD5+ (p less than 0.05) B-cells, together with a greater reactivity for both the CD25 (p less than 0.04) and CD9 (p less than 0.08) antigens in the high proliferative group. According to the prognostic value of the PB S-phase leukocyte count it was seen that patients with low S-phase white blood cell (WBC) numbers displayed a significantly higher survival (p less than 0.03). In addition, multivariate analysis revealed that the S-phase WBC count, although partially related to other clinical and biological prognostic factors, displayed an important independent value in predicting early deaths in patients with B-CLL.