Antibody regulation of hapten-specific granulomas was studied in mice in order to assess the relationship between an anti-idiotypic antibody and granuloma formation. An anti-idiotypic antibody was raised against the idiotype of an azobenzenearsonate (ABA)-specific antibody of A/J mice. The anti-idiotypic antibody was subcutaneously (s.c.) administered to syngeneic mice prior to challenge with ABA-coupled polyacrylamide beads injected into the intestinal wall. The results of such a challenge were assessed histologically for granuloma formation at 24-h intervals. Mice primed with anti-Id antibody and challenged with ABA-linked beads developed epithelioid granulomas at 72 and 96 hr post-challenge. Unprimed mice or mice primed with control antibodies did not develop granulomas when challenged with ABA-linked beads. Moreover, we found that priming with anti-Id antibody intravenously (i.v.) resulted in suppression of intestinal granuloma formation that was similar to that observed previously after priming mice i.v. with ABA-coupled spleen cells (Ginsburg et al., 1982). This study demonstrates the induction and suppression of hapten-specific granuloma formation in the intestine by an anti-Id antibody. The observations indicate a role for the idiotype-anti-idiotype interaction in regulation of hapten-specific granuloma formation, and may have implications for the manner in which the host reacts against self in the autoimmune inflammatory process.