Cell wall components of the pathogenic yeast Candida albicans have been shown to possess significant immunomodulatory activity both in vivo and in vitro. We have previously found that an ethylenediamine (EDA) extract of the Candida cell wall exhibits significant immunosuppressive activity. In an effort to further characterize the immunomodulatory activity of the EDA extract, we attempted to determine the effect of this extract on macrophage phagocytic activity. Our results show that nonelicited peritoneal macrophages treated for 24 or 48 hr with the EDA extract fail to phagocytize Candida yeast cells normally. We have observed that the phagocytosis of Candida is mediated by a combination of lectin-like receptor-, Fc receptor-, and complement receptor-type 3 (CR3)-dependent processes. Results show, however, that the most efficient uptake of this organism is dependent on CR3-mediated phagocytosis. Experiments carried out under various opsonic conditions suggest that the level of CR3-mediated phagocytosis of Candida is depressed following EDA extract treatment. These results show that a substantial mechanism of macrophage phagocytosis is depressed following contact with cell wall components of Candida.