Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1α, MIP-1β, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MlP-la, MIP-1β, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 μg/ml: 26.9 ± 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 μg/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n=2), skin (n=1), uterus (n=3), or tonsils (n=3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2Rβ, CD63, IL-3Rα, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.