mononuclear cells from patients with the hyperige syndrome produce little ige when they are stimulated with recombinant human interleukin4 to investigate whether b cells from patients with the hyperige syndrome are more sensitive to the effects of interleukin4 in vitro than b cells of normal or atopic individuals we stimulated blood mononuclear cells mnc with varying doses of recombinant human interleukin 4 rhil4 and measured supernatant ige concentrations after 18 days of culture geometric mean spontaneous ige synthesis after 18 days of culture without rhil4 was low less than 3 ngml and similar for mncs from nine patients with the hyperige syndrome nine atopic and nine normal subjects as found in our previous studies mncs from the nine atopic and the nine normal donors produced significant and similar quantities of ige geometric mean maximum ige 252 and 187 ngml respectively when mncs were stimulated with rhil4 mncs from both donor groups had similar sensitivity to the concentration of il4 eliciting the ige response in striking contrast mncs from the nine patients with the hyperige syndrome failed to produce significant ige over that produced spontaneously when mncs were stimulated by a wide range of rhil4 concentrations coculture of b cellenriched subpopulations from patients with the hyperige syndrome with t cellenriched subpopulations from nonatopic and atopic donors failed to restore responsiveness to rhil4 the addition of anticd40 monoclonal antibody to mnc cultures did result in enhancement of rhil4 ige synthesis by mncs from patients with the hyperige syndrome but the concentration of anticd40 required to elicit this enhancement was tenfold higher than for control mncsabstract truncated at 250 words