In this study, we compared the susceptibility of Peromyscus leucopus (white-footed mouse), a common natural intermediate host, and Mus musculus, a commonly used experimental model, to infection with larvae of the raccoon ascarid, Baylisascaris procyonis. Three groups of 10 mice of each species were given 50, 250, or 500 infective B. procyonis eggs by gavage. The mice were observed daily for clinical signs of central nervous system (CNS) disease and at necropsy the distribution of larvae in 10 body regions and organs was determined and compared. Clinical CNS disease developed in 57% of P. leucopus and 93% of M. musculus. The average clinical incubation period was significantly longer in P. leucopus (20.6 days postinfection [PI]) than in M. musculus (10.7 days PI), and clinical disease progressed slower in P. leucopus. Significantly fewer larvae were recovered from P. leucopus than from M. musculus. Most larvae were recovered from the anterior carcass and viscera of P. leucopus and from the carcass, head, and brain of M. musculus. CNS invasion was dose dependent in M. musculus but not in P. leucopus. Few or no grossly visible larval granulomas were present in P. leucopus but were abundant in M. musculus. We concluded that P. leucopus was less susceptible than M. musculus to B. procyonis infection, based on a decreased intensity of infection, longer clinical incubation period or lack of clinical disease, slower progression of disease, different larval distribution, and lower tissue reactivity to larvae.