Soluble CD23 (sCD23) has been recognized as an important prognostic parameter in patients with chronic lymphocytic leukemia (B-CLL) at early clinical stages. There is, however, no clear information on its prognostic significance in advanced stages and on its role as an indicator for aggressive or indolent courses of disease. Therefore, sCD23 was measured in the serum of 145 patients at diagnosis and serial determinations were carried out for 8 years in 38 patients. The results indicate that in patients with identical clinical stages at first presentation the disease could take different courses depending on initial sCD23 concentrations below or above specific threshold levels (860 and 5900U/ml). sCD23 higher than these thresholds was associated with faster progression into upper clinical stages. Furthermore, sCD23-doubling time (sCD23-DT) indicated that patients with long DT progressed slowly, while those with short DT had more aggressive disease. Particularly in patients with advanced disease stages, long sCD23-DT indicated development of smoldering disease. Since sCD23 levels reflect total tumor mass, determination of sCD23-DT has probably a better predictive value than lymphocyte doubling time. It appears that B-CLL patients can be divided into different risk categories according to initial determinations of sCD23 and that sCD23-DT is an additional important parameter in predicting disease progression.