We tested the possibility that two phenotypic traits, defective activation of macrophage antileishmanial activities and susceptibility to infection with Leishmania major, were controlled by the same gene. We used P/J (susceptible) and C3H/HeN (resistant) mice to breed F1, backcross (Bx), and F2 mice that were tested individually for both traits, each of which is known to be controlled by a single autosomal gene. We found no correlation between the macrophage defect and cutaneous disease. There was a correlation between development of systemic disease and defective macrophage activation in Bx mice; this correlation, however, was not confirmed in the F2 population.