[en] The lung colonization of MO4 cells, a highly malignant murine cell line, is strongly reduced in syngeneic C3H/He mice by a prior incubation with anti-alpha-galactosyl antibody (alpha-Gal Ab), a natural IgG antibody present in high titers in all normal human sera and specifically recognizing Gal alpha(1----3) structures (alpha-D-galactopyranosyl; alpha-D-Galp). The protective effect is due to a binding of alpha-Gal Ab to alpha-D-Galp end groups of MO4 cells, inducing both an increase in their sequestration into the liver and the spleen and a decrease in their sequestration into the lung. The F(ab')2 fragments of this antibody also exhibit a protective effect by inhibiting the homing of MO4 cells into the lung, without modifying their accumulation into the spleen and the liver. Since both the antibody and the alpha-galactosidase pretreatments of MO4 cells block their subsequent attachment to murine laminin in vitro, we suggest that, in this model, the lung colonization may be dependent on the alpha-D-Galp end groups exposed on the surface of MO4 cells.