n-Hexane and its metabolites are neurotoxic to animals and man. Studies have revealed a progressive neuropathy which affects the distal regions of motor and sensory peripheral nerves. This paper describes efforts to determine whether 2-hexanone or 2,5-hexanedione is more neurotoxic to rats when given in drinking water. Our results show that 2,5-hexanedione is more neurotoxic than 2-hexanone and that it first affects the distal axon. Concentrations of 20 mM produced no effects after 3 weeks but 40 mM increased distal latency after 2 weeks.