Serotype distributions of Listeria monocytogenes in clinical samples and foods often differ. It is unknown whether such differences reflect a variation in the virulence of strains or are due to other factors that are not directly related to the strains' ability to cause illnesses. Fifty-two food and eight clinical isolates of L. monocytogenes were obtained from France, Japan, and the United States. Their pathogenicity in nonimmunocompromised female ICR mice was determined by intraperitoneal (i.p.) injection of the mice with test strains at 10(8) to 10(9) CFU per mouse. Five mice were injected with each Listeria strain and observed for 5 days. Listeria isolates that caused at least one death in 5 days were considered pathogenic. Isolates that caused no deaths in 5 days were considered nonpathogenic. All strains except Listeria innocua and one L. monocytogenes serotype 4b strain (RM3-1) isolated from bovine raw milk were pathogenic to nonimmunocompromised mice. Three food isolates of L. monocytogenes serotype 1/2c were weakly pathogenic to nonimmunocompromised mice, killing a maximum of 50% of mice at 10(8) CFU. Strains with no pathogenicity or reduced pathogenicity were further tested for their pathogenicity to immunocompromised mice. Each strain was inoculated i.p. into five mice at 10(3) to 10(10) CFU per mouse. No deaths of immunocompromised mice inoculated with 10(8) CFU were observed, but 20 to 40% of the mice died when inoculated with 10(9) CFU of L. monocytogenes RM3-1. The three L. monocytogenes serotype 1/2c isolates were also weakly pathogenic to immunocompromised mice, with two of the three isolates killing < or = 60% of mice at doses of < or = 10(8) CFU. The hemolytic activity of the three weakly pathogenic serotype 1/2c isolates was similar to that of pathogenic strains. However, the nonpathogenic strain RM3-1 was not found to be hemolytic on horse blood agar. We have identified several L. monocytogenes strains with reduced virulence levels. Further characterization of such isolates may aid in understanding factors affecting the variation in virulence among strains.