The object was to evaluate the effects of a polyherbal formulation, Immu-21, against cyclophosphamide (CP)-induced chromosomal aberrations (CA) and micronuclei (MN) in mice. CP alone (40 mg/kg, i.p.) produced classical as well as non-classical chromosomal aberrations in mice, and the incidence of CA was significantly more in the CP treated group when compared with that of the control group. Immu-21, which contains extracts of Ocimum sanctum, Withania somnifera, Emblica officinalis and Tinospora cordifolia, was given at 100 mg/kg, daily, over 7 days, and 30 mg/kg daily over 14 days and inhibited both CP-induced classical and non-classical chromosomal aberrations ( approximately 40%-60% of control). A significant increase in MN was also observed in bone marrow erythrocytes of mice treated with CP, and pretreatment with Immu-21 also significantly reduced these. Cytotoxicity was evaluated by estimating the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs). The present results indicate that chronic treatment with Immu-21 prevented CP-induced genotoxicity in mice.