An in vivo micronucleus assay using Balb/C male mice was used to examine antigenotoxic effects of cimetidine (CM) on benzene (BZN) induced genotoxic effects. CM not only has therapeutic and immunomudolatory role, but it has also been shown to protect bone marrow stem cells from radiation induced clastogenic effects. Therefore, in the present study we attempt to investigate the protective effects and possible mechanisms involved in the effects of CM. An 8-week-old male Balb/C mice (22+/-4 g weight) were treated with different doses of BZN (400, 600 and 800 mg/kg body weight), i.p. and sampled at 24, 48 and 72 h after treatment by cervical dislocation. Various doses of CM (10, 15, 30 mg/kg) were used in association with BZN and 1-2 h prior to BZN treatment. Results show that BZN effectively induced micronuclei in polychromatic erythrocytes (PCEs). Application of CM led to a significant reduction of micronuclei in PCEs, i.e. 2-fold after 10 mg/kg and 3-fold after 30 mg/kg CM treatment. Results also indicate CM was more effective when used in combination with BZN. Therefore, results indicate that CM could reduce clastogenic effects of BZN. Although further investigations are needed to reveal the mechanistical background behind the effect, the most probable mechanism involved might be free radical scavenging. This mechanism might be associated with amplification of glutathione system and cytochrome P-450 inhibition.