Background: A major predictor of childhood atopy is the concentration of IgE in the cord blood, but whether the source of cord blood IgE is maternal or fetal remains unclear. Objective: We sought to determine the pattern of in situ IgE production during ontogeny. Methods: Ninety-seven fetal, 142 natal, and 96 childhood samples were analyzed by using reverse transcription PCR for transcription of VDJCϵ, Iϵ, and CD23. Thirty-eight fetal liver samples were analyzed for the IL4RA genotype. Results: IL-4R⍺, CD23a, CD23b, and sterile Iϵ transcripts were present as early as 8 weeks’ gestation. VDJCϵ transcripts were found in second-trimester fetal liver and third-trimester cord blood, although they were rare. VDJCϵ transcripts were more common in the blood of children 9 months and older. Sequence analysis suggested that fetal VDJCϵ was the product of selection. All fetal livers actively transcribing Iϵ, VDJCϵ, and IL-4R⍺ contained at least one copy of the atopy-associated IL4RA*A1902G polymorphism. Conclusion: The human fetus contains B cells that are primed to undergo IgE class switching from the earliest stages of ontogeny and can produce endogenous IgE by 20 weeks’ gestation. However, IgE-producing cells are rare until 9 months after birth. (J Allergy Clin Immunol 2000;106:911-7.)