The effect of enzyme induction on the metabolism of bis(2- methoxyethyl)ether (111966) (diglyme) was studied in rats. Male Sprague-Dawley-rats were administered 5.1 millimoles per kilogram (mmol/kg) diglyme or 0.1 percent phenobarbital (PB) in their drinking water for 22 days. The effects on hexobarbital sleeping time were evaluated. Other rats were pretreated with 5.1mmol/kg labeled diglyme or 0.1 percent PB administered in their drinking water for 22 days, and then given a single oral dose of 5.1mmol/kg carbon-14 labeled diglyme. Urine samples were collected at 6 to 96 hours post dosing and analyzed for diglyme metabolites. PB and diglyme caused significant decreases in hexobarbital sleeping time, PB showing the greater effect. Pretreatment with PB or diglyme did not significantly affect cumulative excretion of carbon-14 activity. Cumulative excretion of methoxyacetic-acid (625456), a minor metabolite, was significantly increased by both phenobarbital and diglyme, phenobarbital showing the greater effect. The authors conclude that pretreating rats with diglyme or PB increases the extent of cleavage of the ether bond in diglyme, forming 2- methoxyethanol, a precursor of methoxyacetic-acid, a putative reproductive toxicant. The possibility of altered metabolism and toxicity resulting from a shift from a major to a minor pathway may be an important consideration when assessing the risk of occupational exposure to diglyme or similar aprotic glycol ethers.