Carrageenan, a sulfated polyanionic polysaccharide, is commonly used to induce inflammation in experimental animals, and this model is used to screen for the effectiveness of antiinflammatory drugs. Carrageenan-induced inflammation has been attributed to a variety of autocoids including histamine, bradykinin, complement, superoxide, and prostaglandins. This study examines the effects of carrageenan on human PMN in a serum-free system. Carrageenan was found to stimulate the reduction of NBT by PMNs without stimulating membrane depolarization, oxygen consumption, H2O2 production, or myeloperoxidase secretion. Carrageenan stimulates a heat-labile, NBT-reducing system which is unassociated with the usual stimulus-response coupling seen with other PMN activators such as PMA, FMLP, and zymosan.