The effects of 25 recently discovered plant lectins on cell proliferation and enzyme release were compared to those of previously known lectins on rat microglia and astrocyte cell cultures. A dose-dependent proliferation of microglial cells, but not of astrocytes, was induced by seven lectins, whereas five lectins showed dose-dependent cytotoxicity on both microglia and astrocyte cell cultures. The activity of gelatinase B (MMP-9) was strongly increased in microglial cells by the aforementioned seven lectins, by concanavalin A, and by phytohemagglutinin (PHA-E4), whereas gelatinase A (MMP-2) remained at constitutive levels. The five cytotoxic lectins decreased the activity of gelatinase B in microglia and of gelatinase A in astrocytes, in a dose-dependent manner. The lectin wheat germ agglutinin induced a decrease in gelatinase B activity in microglia, but stimulated gelatinase A and B activity in astrocytes. These results indicate that lectins possess neuromodulatory effects that may motivate the study of their effects on central nervous system (CNS) function in vivo. This, in turn, may lead to better insight into whether lectin or lectin-like molecules can interact with glial cells, and whether they have a role in acute toxicity and in multifactorial diseases in which environmental factors may play a role.