The reverse haemolytic plaque assay was developed to measure antigen (AgE or rye grass I)-specific IgE-plaque-forming cells from the peripheral-blood lymphocytes of ragweed- and grass-allergic patients. The anti-IgE-developing antisera was shown to be isotype-specific, and the response of the assay was inhibited by 52% by the addition of 10 pg of antigen. In addition, the assay was shown to have a reproducibility (s.d.) of 15%. The blood lymphocytes from all fifteen atopic (grass and ragweed) patients were shown to form antigen-specific IgE-plaque-forming cells during the pollen season (mean value 115 cells) and up to 6 months after the season (mean value 56 cells). Cycloheximide appears to block the formation of the plaque-forming cells. This method appears to be sensitive and reproducible enough to study in vitro IgE antibody synthesis of peripheral-blood lymphocytes from atopies.