The validity of the clinical staging of Jaksic and Vitale for chronic lymphocytic leukemia (CLL), designated total tumor mass score (TTM), was tested in 130 consecutive and previously untreated patients followed at our institution over a 15-year period. The analysis, extended to the whole population, confirmed the prognostic value of the TTM score. Patients with a high TTM (greater than 9.0) had an expected median survival (EMS) of 30 months; those with a low TTM (less than 8.9) had an EMS of 129 months (P less than 0.001). The prognostic value of TTM remained even after adjustment was made for age, sex, lymphocyte count, TTM distribution pattern, bone marrow failure, and response to therapy. Taking into account the value of the TTM score, patients of the intermediate risk group (stage II of Rai et al.) could be divided into two subgroups with a different prognosis (EMS 200 vs. 32 months; P less than 0.005). When used as a continuous quantitative parameter the TTM score may help to define response to therapy. In this study TTM response to therapy was significant for prognosis (P less than 0.001), and there seems to be relationship between the degree of response and survival probability.