We have demonstrated that reovirus type 1, but not type 3, generates serotype-specific immunologic tolerance for DTH responses following oral administration of UV-inactivated virus. As shown by adoptive transfer experiments, the tolerance is secondary to the generation of viral-specific suppressor T cells that are present in spleen and mesenteric lymph nodes. No tolerance was generated when live virus was administered orally. Using recombinant viral clones, it was found that 2 viral gene products were required for tolerance induction; serotype specificity is a property of the viral hemagglutinin (the product of the S1 dsRNA segment). The inability of type 3 reovirus to induce suppression following oral administration is a property of the mu 1C polypeptide (the product of the M2 dsRNA genome segment).