We examined the expression of (TG)-A--L specific Ir genes in helper T cells using T cells from low responder leads to (B10, high responder x low responder) F1 chimeric mice. In this paper, the low responder strain studied was B10.M, H-2f. B10.M T cells from these chimeric animals do not help anti-TNP-(TG)-A--L responses, even though they have matured in a high responder thymus and been primed and challenged with antigen on high responder Mphi and B cells. These findings indicate that in the H-2f haplotype an Ir-gene controlling anti-(TG)-A--L activity is expressed in helper T cells. The findings are in contrast to those we have obtained and previously reported with T cells of another low responder haplotype, H-2a. Taken together with our previous findings that (TG)-A--L specific Ir genes are expressed by B cells and Mphi of both the H-2a and H-2f haplotypes, the results indicate two sites of action for Ir genes, and suggest two different gene products acting at different stages of the response, both of which are defective in H-2f cells, and only one of which is defective in H-2a cells.