Certain synthetic, nonionic, block copolymers of polyoxypropylene and polyoxyethylene are potent immunoadjuvants. While investigating their mechanisms of action, we found that one of these copolymers, L81, induced the expression of macrophage Ia in vivo. L81 is a 2750-Da, linear copolymer with a 43-unit core of hydrophobic polyoxypropylene flanked on each side by 3 U of hydrophilic polyoxyethylene. It induced threefold to sevenfold increases in the proportion of peritoneal macrophages expressing I-A from 5 to 7 days after an i.p. injection of 5 mg. As little as 1 mg caused a twofold increase. I-A density increased with time after injection of L81. Macrophages induced by L81 actively synthesized I-A, showing an 18-fold increase in biosynthetic capacity. Ia induction did not require the presence of mature T lymphocytes, because similar increases in I-A expression were seen in athymic and euthymic mice. L81-induced macrophages were 10-fold more effective than normal macrophages in presenting Ag to a T cell hybridoma. Other functional studies showed that they were primed for the secretion of superoxide ion and could be stimulated in vitro by IFN-gamma and LPS to lyse tumor target cells. These results suggest that the induction of macrophage Ia expression by L81 may play a role in its activity as an immunoadjuvant.