In order to determine the specific structural properties responsible for neurotoxic activity, the comparative neurotoxicity of n-hexane, methyl n-butyl ketone, 2,5-hexanedione, and their relatives was investigated in the peripheral nerves of rats. The maximum conduction velocity of motor and sensory fibres and the motor distal latency of the tail nerves of rats were periodically examined in animals receiving repeated subcutaneous injections of 11 aliphatic monoketone or diketone compounds and their relatives for prolonged periods. A study of the comparative neurotoxicity of n-hexane, methyl n-butyl ketone, and their metabolites showed that 2,5-hexanedione was the most actively neurotoxic. Furthermore, a study of other symmetrical diketones with different carbon numbers showed that 2,4-pentanedione, which is structurally similar to 2,5-hexanedione, possessed a different type of neurotoxic activity than 2,5-hexanedione. Regarding aliphatic monoketone compounds, acetone, 2-pentanone, 2-heptanone, and 2-octanone were confirmed non-neurotoxic for the peripheral nervous system. Evidence from some previous reports, however, suggested that 3-heptanone, 4-octanone, and 5-nonanone might produce neuropathies by being converted to 2,5-diketones under specific conditions.