AbstractMutations of the X‐linked genes Tabby (Ta) in mice and EDA in humans result in developmental and functional abnormalities, primarily in the skin and hair follicles. Although both genes are believed to encode membrane‐associated proteins, it has been suggested that, in the mouse, the mutation is linked to a deficiency of epidermal growth factor (EGF). This study investigated relationships between the skin abnormalities of Ta mice and the EGF signal pathway. The distribution of endogenous EGF in tissues of Ta/Y and +/Y animals was examined and, because of its reported morphogenetic actions and ability to overcome receptor signalling defects in vivo, the effects of exogenous EGF on the hair follicle population were determined. EGF levels were similar in a number of tissues of Ta/Y and +/Y mice, but amounts in Ta/Y submaxillary glands were reduced, probably due to a smaller gland size. Exogenous EGF inhibited hair follicle development and decreased follicle density in both genotypes. It was concluded from comparisons of the distributions of EGF and its effects in skin with those in mice bearing mutations in the EGF signal pathway that the normal phenotype results from interactions between EGF and the Ta peptide in skin.