Basophil responsiveness to histamine-releasing factors (HRF) is limited to cells from atopic donors; this response can be transferred passively to non-reactive hasophits by IgE molecules from the sera of donors who are intrinsically responsive to HRF , Deuterium oxide (D2O) also causes mediator release from the basophils of atopic asthmatic subjects . To assess whether basophil responsiveness is IgE dependent, and, if so, whether this release revealed IgE heterogeneity, we tested the ability of sera from HRF responders (IgE+) and non-responders (IgE -) to sensitize basophils to D2O. Both purified IgE + and unpurified sera from an HRF responder were passively used to sensitize basophils whose IgE had been removed by lactic acid treatment. As a control, an IgE- myeloma-containing serum was used for passive sensitization. In five experiments, histamine release in the presence of 44% D2O was 9 ± 2% and 46 ± 4% using control IgE- and lgE+ sensitized cells, respectively. The non-responder serum, even at higher IgE levels, did not sensitize the cells for D2O release. If the IgE receptors on lactic-acid treated cells were first exposed to serum from an IgE- donor, sensitization to DiO by IgE+ was blocked. The percentage histamine release to D2O was directly related to both the amount of IgE+ used for passive sensitization and the concentration of D2O used for release. These experiments further support the concept of IgE heterogeneity and suggest that the occupancy of IgE receptors on the basophil surface ‘activate’ the cell to make it more responsive to various stimuli.