Patients with the hyper-IgE syndrome have greatly elevated percentages of IgE Fc receptor (Fc epsilon R)-positive B cells, but they have less than 0.1% Fc epsilon R+ T cells (T epsilon cells) and few, if any, Fc epsilon R+ natural killer cells. They also have markedly decreased numbers of IgG receptor positive (Fc gamma R+) T cells (T gamma cells). Patients with the hyper-IgE syndrome resemble in this respect patients with severe atopic dermatitis. Since a portion of T epsilon and T gamma cells of mildly atopic patients react with monoclonal antibody OKT8, they may have a suppressor function. However, whether the low number of T epsilon cells is responsible for the high IgE serum level in hyper-IgE syndrome and atopic dermatitis patients remains to be demonstrated. Attempts to obtain a reliable assay for human IgE synthesis in vitro to investigate the function of Fc epsilon R-positive lymphocytes proved to be difficult. Even isolated B cells from atopic donors seldom produced more than twice the quantity of IgE released from cells incubated in the presence of the protein synthesis inhibitor cycloheximide.