Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human α2-macroglobulin converted to its 'fast' form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both α2-macroglobulin-trypsin and α2-macroglobulin-methylamine inhibited macrophage production of superoxide anion (O2-) while native α2-macroglobulin had little effect except at high concentration. The α2-macroglobulin 'fast' forms, which bind with a Kd of about 8 nM, inhibited 50% generation of O2-(ID50) at a concentration of 7 nM while α2-macroglobulin inhibited O2- production with an ID50 of 141 nM. The 'fast' forms of α2-macroglobulin may play a role in the feedback regulation of inflammatory reactions. © 1983.