Within the genus Listeria, the species L. monocytogenes most frequently causes disease in animals and humans. L. Seeligeri, a species recently described, has been considered experimentally nonpathogenic so far. The authors report the first case of human infection in a previously healthy adult presenting with acute purulent meningitis due to L. seeligeri. The patient recovered promptly after a course of ampicillin and gentamicin, but developed severe neurological sequelae (epilepsy, hydrocephalus) one year after the acute episode. The pathogenic properties of this isolate were investigated in two experimental animal models and the results were as follows. The clinical isolate of L. seeligeri was able to colonize the spleens of adult mice without bacterial multiplication, in contrast to the type strain of L. seeligeri (no colonization) and to a L. monocytogenes strain (colonization and multiplication). Previous infection of adult mice with the clinical L. seeligeri isolate protected moderately against spleen colonization and bacterial multiplication after challenge with L. monocytogenes. No lethal effect was observed after inoculation of suckling mice with the clinical L. seeligeri isolate, in contrast to L. monocytogenes strains. Thus, L. seeligeri, previously described as experimentally nonpathogenic for mice, may in fact be a heterogeneous species regarding its pathogenicity, and include strains that may cause life-threatening diseases in humans.