Cyclophosphamide (CTX) is a chemotherapeutic drug used for treatment of certain solid tumors, lymphomas, and some autoimmune diseases. The antitumor effect of CTX is associated with leukopenia and liver dysfunction. There is an interest in exploring agents that can minimize the adverse effect of CTX without ameliorating its antitumor efficacy. Among the potential agents is a recent study on white button mushroom, which has been found to exert anti-toxic effects. This study was designed to assess the beneficial effects of mushroom extract on the antitumor and toxic effects of CTX. Swiss albino mice were inoculated with intraperitoneal injection (i.p.) of 0.25 x 10⁶ (day 0) of Ehrlich ascites carcinoma (EAC) cells. Mice were treated with a single dose of CTX (200mg/kg) on day 1 or day 7 post EAC inoculation. Agaricus bisporus mushroom extract (666 mg/kg) was administrated (i.p.) on days 8-14 post tumor challenge. The numbers of leukocytes as well as liver function were assessed on day 17. Treatment with CTX on day 7 induced 46% and 37% decrease in the absolute number of monocytes and neutrophils. It had no effect on serum alanine amino transferase activity, while it induced 57% decrease in serum alkaline phosphatase activity. It induced 41% decrease in liver GSH as compared with tumor-bearing mice. Co-administration of mushroom extract with CTX induced 86% decrease in the number of EAC cells, 72% increase in the absolute number of monocytes, 37% increase in the absolute numbers of neutrophils, 57% decrease in serum ALP activity, 100% increase in GPX activity and 35% increase in GSH as compared with tumor-bearing mice. These results indicate to the beneficial effects of mushroom to enhance the antitumor effect of CTX coincided with reduction of its toxic effect.