The activation of T lymphocytes from poly (Glu60Ala30Tyr10)n (GAT)-primed donors by GAT-pulsed nonimmune spleen cells was shown to require identity at the I-1 subregion of the major histocompatibility complex. However, GAT-primed T lymphocytes from (responder x nonresponder) F1 hybrids could only be stimulated to proliferate by GAT bound to high responder or F1 spleen cells but not by GAT bound to spleen cells from the low responder parent. The failure of spleen cells from low responder parental strains to present GAT was shown not to be due to the presence of suppressor cells in either the antigen-presenting or the responding cell populations. These results indicate that control of antigen-presenting cell-T lymphocyte interactions is one site of Ir gene expression.