This study assessed the involvement of phagocytic cells in murine resistance to disseminated candidiasis of endogenous origin. SCID mice and their immunocompetent CB.17 (BALB/c) counterparts were colonized with a pure culture of Candida albicans and treated with an antigranulocyte monoclonal antibody (anti-Gr-1), polyinosinic:polycytidylic acid (poly[I.C]), or both to impair macrophage function in vivo. Candida-colonized SCID mice were more susceptible to disseminated candidiasis after treatment with anti-Gr-1 or poly(I.C) than were CB.17 mice. Histopathology of orogastric tissues demonstrated that combined treatments with anti-Gr-1 and poly(I.C) also enhanced the susceptibility of SCID and CB.17 mice to orogastric candidiasis. These data indicate that macrophages as well as granulocytes play an important role in host resistance to mucosal and disseminated candidiasis of endogenous origin.