In this study we show the inheritance of a CD4(+)CD8(+) peripheral T cell population in the H.B15 chicken strain. A large proportion of alpha beta T cells in peripheral blood (20-40%), spleen (10-20%) and intestinal epithelium (5-10%) co-express CD4 and CD8 alpha, but not CD8 beta. CD4(+) CD8 alpha alpha cells are functionally normal T cells, since they proliferate in response to mitogens and signals delivered via the alpha beta T cell receptor as well as via the CD28 co-receptor. These cells induce in vivo a graft versus host-reaction, providing further evidence for their function as CD4(+) T cells. The CD4(+)CD8 alpha alpha T cell population was found in 75% of the first progeny and in 100% of further progenies, demonstrating that co-expression of CD4 and CD8 on peripheral T cells is an inherited phenomenon. In addition, cross-breeding data suggest a dominant Mendelian form of inheritance. The hereditary expression of CD8 alpha on peripheral CD4(+) T cells in chicken provides a unique model in which to study the regulation of CD4 and CD8 expression.