Serial determinations of adenosine deaminase (ADA) activity in 69 patients with chronic myelogenous leukemia provided a biochemical marker of disease activity. Eighty-nine % of patients in the accelerated phase had an elevation of ADA activity. This elevation was not a direct reflection of an increased absolute blast count. Furthermore, five of seven patients studied serially from the stable phase into the accelerated phase had an increase in ADA activity before the absolute blast count increased. This is the first investigation which clearly demonstrates the potential value of measuring serial ADA activities in a large number of patients with chronic myelogenous leukemia.