The response to an intraperitoneal (i.p.) parasite challenge was compared with that caused by an oral challenge, in five different strains of mice. The results are consistent with the hypothesis that murine susceptibility to toxoplasmosis is route of challenge-dependent as well as strain-dependent. The phenomenon occurs in both sexes and appears to be a recessive trait. The finding that the susceptibility of C57BL/6j mice to oral or i.p. challenge is almost the reverse of that of LACA mice, and that BALB/c mice are resistant to challenge by either route, offers an excellent laboratory model for studies on susceptibility to toxoplasmosis.