This report confirms our previous observation that protein A (PA) of Staphylococcus aureus Cowan I reduces the cyclophosphamide (Cy) induced toxicity. PA treated animals recover quickly from the toxic effects of Cy. We have exhaustively studied the role of specific and nonspecific immunity in the protection of the animals. It was observed that PA helped the animals in the accelerated regeneration of leukocytes of blood (p less than 0.001) and different lymphoid organs like thymus (p less than 0.001), spleen (p less than 0.01) and bone marrow (p less than 0.01). Increased number and function of macrophages was also observed in PA (p less than 0.001) and PA+Cy (p less than 0.001) groups. PA, on one hand enhanced the cell mediated immunity while suppressed the humoral immunity as was assessed by increase in delayed type hypersensitivity response (p less than 0.001) and decreased in plaque forming cells (p less than 0.001), EAC-rosettes (p less than 0.001), hemagglutination (p less than 0.001) and hemolysin titre (p less than 0.05). On the basis of above observations we propose that the immunomodulatory activity of PA helped the animals to remain alive in two ways- (1) by early generation of the cells depleted by the Cy thus helping animals to repair the damaged immune system and fast clearance of the toxic metabolites of Cy (2) by temporarily suppressing the cells responsible for humoral immunity which are more susceptible to Cy metabolites.