The in vitro effect of human recombinant interferon alpha (IFN) alone and in combination were studied on granulomonocytic colony forming units (CFU-GM) from the peripheral blood of 10 Ph 1+ chronic myeloid leukemia (CML) patients and from the marrow of 5 normal or non-leukemic subjects. alpha- and gamma-IFN alone determined a slight inhibition on colony growth with a preferential effect on "pure" macrophagic colonies. At maximum concentration (10(4) U/ml) leukemic colony inhibition was 46 +/- 34% for alpha IFN and 43 +/- 19% for gamma IFN. Culture growth with alpha + gamma IFN in combination were significantly inhibited (up to 96 +/- 4%) with a concentration-related effect. Similar results were obtained with normal CFU-GM. The synergism that was found in vitro is probably relevant for the in vivo therapeutic effects of these compounds in CML and suggest that the combination is worth testing in vivo.