Human recombinant interleukin-3 (hrIL-3) released histamine from human leukocytes in vitro. The histamine release by hrIL-3 significantly correlated with those by anti-IgE, thrombin, and f-met. peptide, but not by A23187. Histamine release by hrIL-3 was a Ca2(+)-dependent reaction, as was that by anti-IgE, although the time course of histamine release by hrIL-3 was slower than that by anti-IgE. Pre-treatment of leukocytes with hrIL-3 decreased the histamine release by hrIL-3 itself, but enhanced the histamine releases by anti-IgE, f-met. peptide, thrombin and A23187. These results suggested that the mechanism of hrIL-3-induced histamine release was different from those of anti-IgE, f-met. peptide, thrombin, and A23187. There was no significant difference between hrIL-3-induced histamine release of leukocytes from asthmatics and healthy controls.