Pretreatment with N,N-dimethylaminoethyl (DMAE) paramylon significantly protected mice from infection by various microorganisms. When mouse peritoneal macrophages were cultured with DMAE-paramylon, they showed morphological change (spreading) and elevated NBT-reducing activity. Macrophages prepared from DMAE-paramylon-treated mice had higher NBT-reducing activity than those from control mice. On the other hand, carboxymethyl paramylon and paramylon sulfate, which did not induce appreciable antimicrobial activity, failed to stimulate macrophage functions. The data suggest a significant role of macrophages in antimicrobial activity induction by cationized glucans.