Peripheral blood lymphocytes from two human donors with elevated serum IgE concentrations were maintained in short term tissue culture preparations. Repeated culture preparations demonstrated that IgE was produced in vitro in amounts that could be measured by the double antibody radioimmunoassay technique. The amount of IgE produced by replicate cultures of cells from a single bleeding of the donor was similar when the cultures were simultaneously prepared. In contrast, IgE production by the same donor's lymphocytes varied when the culture preparations were initiated from separate bleedings. The results of simultaneous cultures of a single bleeding were sufficiently consistent to provide a means of testing the effect of pharmacologic agents on the in vitro production of IgE. Cholera toxin effected a marked reduction in production of IgE by lymphocytes of both cell donors. Isoproterenol showed marked inhibition of IgE production at 10(-3) M but cell viability studies suggested that this may have been due to decreased cell viability. At lower, nontoxic concentrations of isoproterenol (10(-4) M-10(-6) M) slight but definite inhibition of in vitro IgE production was evident. This inhibition was more pronounced subsequent to the first 24 hr of exposure of the cells to isoproterenol.