Many studies have demonstrated differences in the resistance of strains of mice to infection by Leishmania donovani, Salmonella typhimurium, and Mycobacterium bovis BCG; this resistance/susceptibility phenotype seems to be controlled by a single gene. The present study investigated the susceptibility of liver, lung, peritoneal, and spleen macrophages to infection by L. donovani promastigotes in vitro; the objective was to determine if the susceptibility of animals was expressed by their macrophages when infected in vitro. This study indicated that the Lsh phenotype was only expressed by liver macrophages. The liver macrophages of the susceptible C57BL/6J strain were significantly more phagocytic than those of the resistant C57L/J strain; infection affected the phagocytic activity of the macrophage population. These results indicated that only liver macrophages can express the Lsh gene. Recognition of expression is in part due to its effect on the phagocytic activity of the macrophages.