Propylene glycol (1,2-propanediol) is a solvent in numerous pharmaceuticals and a major preservative and source of carbohydrates in processed foods. In mammals, propylene glycol is metabolized similar to ethanol, proceeding via hepatic alcohol and aldehyde dehydrogenases to lactate, which can then enter gluconeogenesis. We observed that cats ingesting 1.6 gm of propylene glycol/kg body weight/day developed increased anion gap. To investigate this further, we measured D- and L-lactate concentrations in these cats; we also measured D-lactate in cats ingesting high doses of propylene glycol (8.0 gm/kg). While L-lactate actually decreased throughout the 35-day course of propylene glycol feeding, D-lactate levels were significantly increased on a dose-dependent basis and correlated positively with anion gap. In cats ingesting the high dose of propylene glycol, D-lactate concentrations were as high as 7 mmol/liter, levels associated with encephalopathy in humans. Indeed, this group of cats developed depression and ataxia, consistent with intoxication by D-lactate. These findings are significant not only for animals ingesting diets which contain propylene glycol, but for humans who receive propylene glycol-containing medications.