We investigated the effect of all-trans retinoic acid (ATRA) alone and in combination with interferon-alpha (IFN-alpha) on the granulocyte-macrophage (GM) colony formation of peripheral blood progenitors isolated from patients with chronic myeloid leukemia (CML) (n = 12) or other myeloproliferative disorders (n = 10) as well as from healthy controls (n = 7). The ATRA or IFN-alpha alone inhibited slightly, but not significantly, the GM colony growth in CML. Granulocyte-macrophage colony formation decreased significantly (P<0.05) when ATRA and IFN-alpha were combined (114 +/- 96 versus 74 +/- 53 colonies/10(4) mononuclear cells). The combination did not have any inhibitory effect on the other MPDs. In healthy controls, ATRA or IFN-alpha alone or their combination stimulated GM colony growth, the increase being from 22 +/- 9 to 39 +/- 16 colonies for ATRA (P<0.05), up to 47 +/- 12 colonies for IFN-alpha (P<0.05) and up to 50 +/- 19 colonies for the combination (P<0.05). In conclusion, ATRA combined with IFN-alpha inhibits GM colony growth in CML. This combination may be worth testing clinically as a treatment of CML.