A tryptic peptide of bovine beta-casein (amino acid residues 184-202) was used as a model antigen to investigate how the relative position of the (helper) T cell and B cell determinants on a protein antigen influences the antibody response. Immunization with the peptide elicited a considerably higher anti-peptide response in the C3H/He strain than in the C57BL/6 strain, despite the fact that the C57BL/6 T cells showed higher reactivity than the C3H/He T cells. The T cell and B cell determinants of the peptide were identified in these two strains. Each strain recognized a single B cell determinant and a single T cell determinant. In the C3H/He strain, the T and B cell determinants were located apart from one another, while the T and B cell determinants of the C57BL/6 strain were located in a region close each other. The results suggest that the level of an antibody response depends on the topological relationship of the T cell and B cell determinants on the antigen molecule.