In cynomolgus monkeys, twice daily subcutaneous injections of recombinant human interleukin-6 (rhlL-6) at doses of 5 to 80 μg/kg/d for 14 consecutive days caused dose-dependent increases in platelet count, usually continuing for more than 1 week after cessation of the injections. The count reached a level apprxoimately twofold or more above the preinjection level even at 5 jug/kg/d, and at doses of more than 20 jug/kg/d, the increase became biphasic with a higher second peak 3 days after cessation of the injections. Morphologic analysis of the bone marrow after the 7 day-injections with 80 μg/kg/d revealed a marked increment in size of megakaryocytes compared with control, indicating the promotion of megakaryocyte maturation. Other changes attributable to the rhlL-6 treatment include dose-dependent loss of body weight, anemia, neutrophilia and monocytosis, elevation of serum C-reactive protein and alpha-1 acid glycoprotein levels, and decrease of serum albumin; all of which returned to normal within 1 week after cessation of the injections and were tolerable at doses of less than 10 jug/kg/d. These findings suggest that rhlL-6 may be an effective strategy for the treatment of thombocytopenia.