Human rIL-3 induces histamine release from some human basophils, with cells from atopics responding to a greater extent than non-atopic donors. The dose response curves were highly variable. IL-3 was active on purified basophils and the release process was slower and required more calcium than anti-IgE. Removal of surface IgE from basophils rendered them unresponsive to IL-3. The response could be restored by passive sensitization of basophils with IgE+, IgE known to bind histamine-releasing factors, and not IgE-, IgE unreactive with histamine-releasing factors. Thus, IL-3 uncovers IgE heterogeneity. IL-3 does not, however, directly interact with IgE+. Rather, passive sensitization with IgE+ or stimulation of basophils with low concentrations of several secretagogues renders the cells sensitive to IL-3. IL-3 may well play a pro-inflammatory role by potentiating the effects of IgE+ or various secretagogues.