The effect of Cyclophosphamide (Cy) on erythrophagocytosis carried out by peritoneal exudate cells (PEC) was evaluated. The results indicate that the treatment of BALB/c mice with a single high dose of Cy (200 mg/kg) increases the capability of PEC to ingest sensitized sheep red blood cells. Cy not only increases the percentage of PEC with engulfed erythrocytes, but also augments the activity of individual phagocytes. This effect is exerted upon both mononuclear and polymorphonuclear cells and is probably due to the activation of receptors for the Fc fragment of IgG on PEC membranes, as unsensitized sheep erythrocytes are not phagocytized. Considering that Cy is one of the most used alkylating agents in treatment of immunological disorders and cancer chemotherapy, this enhancing effect on phagocytosis may be important in the regulation of host defense mechanisms.