Genetic aspects of IgE levels were studied in three large pedigrees, many of whose members had atopic sensitivities to ragweed. Data on 184 persons (80 M, 104 F) were analyzed by the methods of Elston and Stewart after logarithmic transformation and appropriate adjustment for sex and age effects. Several modes of were fitted to the data. The environmental model (of equal transmission frequency for all genotypes) clearly did not fit the data (χ2 23.03, df 3); this suggested a strong hereditary involvement in IgE distribution. High IgE levels being determined by a dominant allele gave the best fit among the hypothesis examined in pooled data. Under a pure polygenic model, the estimated heritability was 49.5%. Using a mixed model of major gene and polygenic transmission (in an analysis which approximates, but is biased toward inflating the major gene component) polygenic inheritance was found to be 11%, but has no significant improvement over the major gene model. When families are analyzed separately, there was evidence of significant heterogeneity among families. The genetic picture was blurred, with one family favoring recessive inheritance of high IgE levels, one with no clear mode, and the third leaning slightly in favor of dominant inheritance. This suggests that the mechanism is not as simple as was thought and that there may be either two alleles or one gene involved in the determination of IgE levels. The findings are consistent with IgE levels being genetically determined with heritability estimated to be about 50%.