Abstract TCR-β (T cell receptor-β-chain) transgenic mice have altered lymphocyte development. TCR-β transgenic mice are hyporesponsive to alloantigens in vivo and are deficient in γδ T cells. In order to begin a study of the relationship between a deficiency of alloreactive γδ cells and the defective function of in vivo alloantigen recognition, we analysed the γδ T cell development in TCR-β mice. The presence of the TCR-Vβ8.2 chain transgene is associated with inhibition of γ chain gene rearrangement. In order to determine how the presence of the TCR-β transgene affects γδ T cell development, γδ T cells were studied in the skin, intestine and spleen. TCR-β mice have dramatically reduced numbers of γδ T cells in the spleen and moderately reduced numbers of γδ T cells among intestinal intraephithelial lymphocytes. In contrast, these mice have normal numbers of γδ dendritic epidermal cells (DEC). These selective deficits could be due to the developmental regulation of transgene transcription during fetal life. We examined transcription of the TCR-β transgene in the fetal thymus and found that the TCR-β transgene is first transcribed at high levels on day 16 of fetal life, after DEC have already migrated from the thymus to the epidermis. Furthermore, mRNA from the transgene was detected in DEC, ruling out the formal possibility that DEC bear a γδ receptor only because they are incapable of expressing the transgene. The expression of the transgene is temporally associated with inhibition of further TCR gene rearrangement and this developmental sequence may be responsible for the selective tissue deficits of γδ T cells.