Male rabbits were intravenously injected with 2,5-hexanedione or 2,5-hexanedione plus acetone. A toxicokinetic analysis showed that a two-compartment model satisfactorily described the kinetics of 2,5-hexanedione in rabbits. Simultaneous dosing with acetone altered the toxicokinetic model which best described the plasma concentration versus time data. The model-independent parameter body clearance, calculated according to the trapezoidal rule, showed a decrease in the body clearance of 2,5-hexanedione in rabbits simultaneously injected with acetone. The results suggest that toxicokinetic interference may partly explain the neurotoxic potentiation of that which occurs in 2,5-hexanedione-induced axonopathy as a response to simultaneous exposure to acetone.