Normal adult BDF1 mice were injected sc with 1 or 10 micrograms/kg/day of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF; specific activity 3.9 x 10 (7) U/mg) for periods up to 11 weeks. After 1, 3, 7, 9, or 11 weeks, groups of three mice were killed and various hematological parameters were evaluated. Such treatment induced a sustained increase in the number and phagocytic activity of peritoneal macrophages, increased weight and cellularity of the spleen, and increased numbers of lineage-restricted precursor cells and multipotent stem cells in the spleen. No significant differences in blood cell numbers or differential counts were observed during the experiment. Femoral granulocyte-macrophage colony-forming cells (GM-CFCs), mixed-lineage colony-forming cells (Mix-CFCs), and 7-and 12-day spleen colony-forming units (CFU-S) were increased in the first week of treatment, but returned to normal (or subnormal levels) later. Examination of histological preparations of liver, lung, skin, ileum, thymus, Peyer's patches, kidney, skin, and brain revealed no differences from control preparations. Mast cell numbers were not increased in any of these tissues. Despite continuing treatment, most hematological parameters normalized upon prolonged rmGM-CSF treatment. The reasons for this are unclear but are not apparently due to the presence of inhibitory factors in the blood of treated mice. The results indicate little evidence of side effects during prolonged therapy with doses of rGM-CSF commonly used in clinical situations.