Twenty-two species of lectin were tested for their ability to induce interferon (IFN) in mouse spleen cells. Twenty-two species of lectins representing four groups, based on competition patterns with monosaccharides, were examined for their ability to induce IFN in cultured mouse spleen cells. The lectins, all belonging to the third group (concanavalin A, succinylated concanavalin A, Lens culinaris lectins type A and B, and poke weed mitogen) induced IFN mainly composed of IFN gamma. They were either T cell or T/B cell mitogens. Five nonmitogenic lectins, Lotus tetragonolobus seed lectin, crude and type II lectins of Ulex europeus, Bandeiraea simplicifolia type II and Salanum tuberosame lectins, and wheat germ agglutinin belonging to either the first or the third group, induced IFN beta. The production of IFN during stimulation IFN beta- and IFN gamma-inducing lectins followed different kinetic curves. WGA induced IFN in circulation when injected i.p. in mice, and a peak titer was found 2 hr after inoculation.