Human blood basophils were treated to remove resident IgE, and passively sensitized with mixtures of ragweed antigen E-specific and non-specific IgE under receptor-saturating conditions. At a ratio of about 0.005 (0.5%) specific IgE or higher, maximal histamine release was observed, but below this a progressive decrease occurred. With leucocytes of four donors, minimal ratios producing mediator release above background varied from 0.001 to 0.00034, which was roughly inversely related to the number of IgE receptors per basophil. This indicated that for these donors' cells a similar number of specific IgE molecules was required for histamine release, and calculation showed the numbers to be 30-55, despite a five-fold difference in total numbers of IgE receptors between different donor basophils. Therefore, it could be estimated that the minimal number of bridges required for basophil activation was to the order of 10-15, depending on whether divalent or trivalent bridges were involved. Since percentage histamine release and percentage degranulated cells were highly correlated after suboptimal sensitization, individual cells or subsets of basophils were apparently differentially responsive. This is consistent with other evidence of functional heterogeneity and that histamine release by individual cells is an all or none process.