A monoclonal anti-IgE antibody was obtained that reacted with some IgE myeloma proteins and with all but a few normal sera. Family studies proved that a genetic marker of IgE had been detected. This allotype, called Em(1), segregates in association with certain Gm-Am haplotypes. The available quantitative evidence warrants the conclusion that human IgE has genetic variants, but no subclasses. Samples from various populations of five continents, representative for the respective prevalent Gm-Am haplotypes, were tested for Em(1). Em(1) was absent mainly in haplotypes carrying A2m(2) and G2m(n). These closely linked genes are located in a chromosomal region that comprises the gamma 2-gamma 4-epsilon-alpha 2 CH genes. A hypothesis for the generation of Em(1) is given.