To examine the role of T cell subpopulations in an acute graft-versus-host (GVH) reaction, gamma delta T cells and alpha beta T cells expressing one of the two prototypic V beta families were negatively isolated from adult blood samples and injected into allogeneic chick embryos. CD4+ alpha beta T cells expressing either V beta 1 or V beta 2 receptors were equally capable of inducing acute GVH reactions, consistent with the idea that alpha beta T cell alloreactivity is determined by CDR3 variability. By themselves, the gamma delta T cells were incapable of inducing GVH reactions. However, host gamma delta T cells were recruited into the donor alpha beta T cell-initiated lesions, where they were activated and induced to proliferate. The data suggest that gamma delta T cells may play a secondary role in GVH reactions.