131 patients with Philadelphia (Ph') chromosome positive chronic myelogenous leukemia (CML) were treated with interferon (IFN) alpha or a combination of IFN alpha and IFN gamma. In study 1, 13 not pretreated and 41 pretreated patients, 48 in chronic phase disease, 6 in accelerated phase, received 4×106U/m2IFN alfa-2b initially. After achievement of hématologic remission, the individually minimum effective dose was used for maintenance. There was no response in acute phase disease. Of the 48 patients with chronic phase disease, 22 achieved a hématologic remission (HR), 13 a partial HR (PHR), and 13 did not respond (NR) to IFN. No major cytogenetic response occurred in these patients, but two patients achieved a major molecular response in Southern blots, whereas PCR tests were positive. In a further randomized study, CML patients without prior therapy were treated initially with 4×106U/m2IFN alpha alone (arm A) or in combination with 50μg IFN gamma (arm B). For maintenance, the maximum tolerable dose of IFN alpha was given (up to 10×106U/day). Thirteen patients in arm A (54%) and 14 (56%) patients in arm B achieved a HR, 7 patients (29%) in arm A and 6 patients (24%) in arm B a PHR. No response could be induced in 4 patients (17%) of arm A and 5 patients (21%) of arm B. Major cytogenetic responses were observed in 5 (20%) patients of arm A and 5 patients (20%) of arm B. Major molecular responses were observed in 3 patients of arm A and 5 patients of arm B. A single negative PCR in a sample of one patient from arm A was followed by a molecular relapse without recurrence of disease. A significant advantage of the combination could not be substantiated. The study had to be terminated because of two deaths in arm B probably due to cumulative toxicity of the different IFNs. In study III, all patients were pretreated and received a combination of IFN alpha and IFN gamma following the protocol of study II, arm B. Here, HRs occurred in 15 patients (54%), PHRs in 7 (25%), and 6 patients (21%) were NR. No complete cytogenetic response was achieved in 16 evaluable patients, but major molecular responses were demonstrated in samples of 2 patients. One patient had a negative PCR result at a single time point.