Mice injected i.p. with RB6-8C5 mAb experienced a profound depletion of neutrophils in the bloodstream and spleen and significant impairment of their resistance to experimental infection with Listeria monocytogenes. Control mice survived i.v. inoculation with 5 x 10(4) L. monocytogenes; whereas, most RB6-8C5 mAb-treated mice inoculated i.v. with as few as 10 L. monocytogenes died within 6 days. RB6-8C5 mAb treatment was particularly deleterious when given within the first 24 h after i.v. inoculation with L. monocytogenes; however, some adverse effect was observed even when administration was delayed until 3 or 5 days after bacterial inoculation. Histopathologic examination of the livers of RB6-8C5 mAb-treated mice revealed necrotic foci that were characterized by few inflammatory cells and massive numbers of Gram-positive bacteria within hepatocytes. Additional evidence that the effects of RB6-8C5 mAb administration were chiefly due to neutrophil depletion include: 1) the effects of RB6-8C5 mAb treatment occurred more rapidly than what is generally seen in mice treated with anti-T cell mAbs, 2) similar results were observed with normal and scid mice, 3) RB6-8C5 mAb administration did not diminish delayed-type hypersensitivity nor the ability of spleen cells from immunized mice to transfer resistance, and 4) natural killer cell activity was unaffected by RB6-8C5 mAb administration. The results of this study provide additional evidence in support of the importance of neutrophils in the early stage of innate resistance to murine listeriosis.