BACKGROUND & AIMS: Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs. METHODS: Dogs were given bacterial or porcine lipase and 3 diets: a 48% carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low-fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet (66%/18%/16% and 21%/43%/36% calories). RESULTS: With the standard diet, coefficient of fat absorption increased dose-dependently with both lipases (P < 0.05), but more fat was absorbed with porcine lipase (P < 0.05); 600, 000 IU of bacterial lipase (240 mg) and 300,000 IU of porcine lipase (18 g) nearly abolished steatorrhea. With 300,000 IU of bacterial lipase or 135,000 IU of porcine lipase, fat absorption was greater with the high-fat and -protein diet (P < 0.05 vs. low-fat and -protein diet). There were no interactions among carbohydrate, fat, and protein absorption. CONCLUSIONS: Correcting steatorrhea requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat and high-protein diets optimize fat absorption with both enzymes. High-fat diets with bacterial or porcine lipase should be evaluated in humans with pancreatic steatorrhea.