The inhibition and aging of acetylcholinesterase (AChE) in fingerling channel catfish(Ictalurus punctatus)brain tissue was studied after single in vivo exposures to high levels of chlorpyrifos (0.25 mg/L), chlorpyrifos‐oxon (7 μg/L), parathion (2.5 mg/L), or paraoxon (30 μg/L). Exposure to both parent compounds produced identical initial inhibition (95%), but in the later sampling times there was significantly more inhibited AChE in the chlorpyrifos‐treated fish than in the parathion‐treated fish (47% and 28%, respectively, on d 16). There were higher levels of aged AChE following chlorpyrifos exposure than following parathion exposure, but differences were not significant. Exposure to both oxons produced initial inhibition greater than 90%, and patterns of recovery and aging were statistically similar between both compounds; no significant inhibition was observed after d 11. The similar patterns of inhibition, recovery, and aging between the two oxon treatments, which have similar lipophilicities, suggest that the greater amount of AChE inhibition and aging observed in the chlorpyrifos‐treated fish compared with the parathion‐treated fish probably results from the higher lipophilicity of chlorpyrifos than of parathion. Overall, the prolonged brain AChE inhibition exhibited in catfish exposed to phosphorothionates is not the result of aging of the inhibited enzyme but is the result of either a slow rate or a lack of spontaneous reactivation.