Accumulation of primary Abs against two distinct epitopes on a designed polypeptide, MEP-1, was examined. The early primary response was predominantly against a C-terminal epitope (MEP 77-100), although subsequent maturation established an epitope within the N-terminal half (MEP 17-31) as the immunodominant one. Inversion of immunodominance correlated with the inability of anti-MEP 77-100 B cells to interact productively with T cells, which consequently received reduced help. Interaction between epitope-specific B and T cells was found to be attenuated in the presence of early primary anti-MEP-1 antiserum, and the extent of inhibition was directly proportional to the level and affinity of epitope-specific Igs. Therefore, it seems that early primary Abs to a multideterminant Ag selectively down-regulate maturation of epitope-specific primary humoral responses.