Synthetic polyol-based lubricating oils containing 3% of either commercial tricresyl phosphate (TCP), triphenylphosphorothionate (TPPT), or butylated triphenyl phosphate (BTP) additive were evaluated for neurotoxicity in the adult hen using clinical, biochemical, and neuropathological endpoints. Groups of 17–20 hens were administered the oils by oral gavage at a “limit dose” of 1 g/kg, 5 days a week for 13 weeks. A group of positive control hens was included which received 7.5 mg/kg of one isomer of TCP (tri-ortho-cresyl phosphate, TOCP) on the same regimen, with an additional oral dose of 500 mg/kg given 12 days before the end of the experiment. A negative control group received saline. Neurotoxic esterase (NTE) activity in brain and spinal cord of hens dosed with the lubricating oils was not significantly different from saline controls after 6 weeks of treatment. After 13 weeks of dosing, NTE was inhibited 23 to 34% in brains of lubricant-treated hens. Clinical assessments of walking ability did not indicate any differences between the negative control group and lubricant-treated hens. Moreover, neuropathological examination revealed no alterations indicative of organophosphorus-induced delayed neuropathy (OPIDN). In hens treated with the positive control, significant inhibition of NTE was observed in brain and spinal cord at both 6 and 13 weeks of dosing; this group also demonstrated clinical impairment and pathological lesions indicative of OPIDN. In conclusion, the results of the present study indicated that synthetic polyol-based lubricating oils containing up to 3% TCP, TPPT, or BTP had low neurotoxic potential and should not pose a hazard under realistic conditions of exposure.