The encouraging therapeutic results attained with the purine analogue CdA in patients with previously treated CLL prompted us to assess its potential in untreated CLL patients. Nineteen patients, 13 males and six females, median age 65 years (range 27-75), with previously untreated CLL were given monthly courses of CdA, 0.12 mg/kg/day as 2-h i.v. infusions for 5 days, until maximum response or excessive toxicity. Five patients with Binet's stage A, 10 with stage B and four with stage C CLL entered the study. After a median of five courses of CdA (range 1-9) nine complete responses (CR = 47%, CI: 24-69%), five partial responses (PR = 26%, CI: 7-46%) and five failures (= 26%, CI: 7-46%) were recorded. In five complete responders and in one partial responder cytofluorometric analysis of blood and/or bone marrow failed to demonstrate a residual clonal B cell population. A search for residual disease by PCR technology and by immunostaining of bone marrow biopsies however disclosed residual leukemic cells in these six cases. Adverse reactions included fever of unknown origin (n = 3), pneumonia (n = 2), herpes simplex infection, herpes zoster, an anal abscess, a cutaneous rash, autoimmune hemolysis and mental disturbance (one patient each). In this small cohort, neither age, stage, blood counts, cytogenetics or pattern of bone marrow infiltration at inclusion were predictive for response. From these preliminary data, we conclude that CdA has remarkable short-term efficacy in patients with previously untreated CLL. However, toxicity is not negligible and long-term benefit from therapy with CdA still has to be established.