Patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) and on interferon (IFN)-alpha-2c treatment for at least two months were entered in the present pilot study. IFN-alpha treatment was maintained identically and cytosine arabinoside (Ara-C) was added at monthly cycles of 10 mg/m2/day for ten days subcutaneously. In the case of a leukocyte nadir above 10 G/l, the Ara-C dose was increased to 20 mg/m2/day for 10 days per month. Ten of the eleven patients entered in this study were evaluable for toxicity and response. They received a total of 87 IFN-alpha/Ara-C cycles (3-14/patient). Five patients received 1-5 cycles with Ara-C dose intensification to 20 mg/m2/day. The following gastrointestinal and hematological toxicities were attributable to Ara-C, as they had not been observed in these patients during the preceding IFN-alpha monotherapy period. Gastrointestinal side effects consisted of nausea grade 1 (n = 5) and diarrhea grade 2 (n = 1). Hematotoxicity was observed in eight patients, grade 1 in five patients and grades 2, 3 and 4 in one of the patients each. Both episodes of grades 3 and 4 toxicity were seen during dose escalation to 20 mg/m2. Small cytogenetic responses (4-14%) were observed in 3 patients and a larger one (50%) in one patient, hematological improvement or stable disease in an additional three patients. These preliminary data suggest that the combination of IFN-alpha and low-dose Ara-C is active in inducing cytogenetic responses in CML patients at an acceptable rate of toxicity and therefore warrant further investigation.