Cochlear disruptions induced by toluene were shown in the rat but not in the guinea pig. To better understand the differences between species, three investigations were carried out to study (1) the blood affinity and the pulmonary uptake of the solvent, (2) its clearance and (3) its urinary elimination in both species. The blood affinity of toluene was +44% higher in the rat than in the guinea pig (14.4μg/g versus 10μg/g). Similarly, the pulmonary uptake of toluene was approximately 46.5% more efficient in the rat than in the guinea pig (75.4μg/g versus 40.3μg/g) after 3h inhalation of 1500ppm toluene. Therefore, the physicochemical composition of the blood could explain the difference in the uptake performances between rats and guinea pigs. The clearance of the toluene showed that 10min after an intravenous administration of 400μL of vehicle containing 28μL (43mgkg(-1)) of toluene, the solvent concentration was approximately threefold higher in the rat than in the guinea pig blood. The last experiment was carried out to compare the concentrations of the urinary metabolites. The concentrations of o-cresol, hippuric and benzyl mercapturic acids measured in the urines were different before and after the toluene injection. These data give evidence for large differences of toluene uptake and metabolism between rat and guinea pig. Therefore, it seems reasonable to claim that guinea pigs cochleas are not susceptible to toluene as the blood burden of solvent does not reach the concentration required to induce permanent damages.