We have synthesized several polyanionic polymers for biological evaluation and to probe the mechanism of macrophage activation. We have determined that, while the molecular weight of the polymers is toxicologically important, the hydrophlicity, chain rigidity, and surface charge play a significant role with respect to the degree of macrophage activation. Macrophages elicited with polyanionic polymers with hydrophobic groups were cytotoxic to Lewis lung carcinoma both in vitro and in vivo. However, macrophages stimulated by polymers with high carboxylic acid group density but little hydrophobicity did not demonstrate significant antitumor activity.