Effects of low-calorie semistarvation diets on gastrointestinal and cardiac organ systems were studied. Male Sprague Dawley rats were divided into two groups, Group I, control (C) and Group II, semistarvation (SS), and maintained on a diet designed after low-calorie modified-fasting regimens in popular use. C animals consumed this diet ad libitum; SS animals received 23% of the total calories of C but the same ratio of calories from protein, carbohydrate, and fat and the same quantity and quality of all essential nutrients. Final weights of total body, heart, liver, and small intestine were lower in SS than in C animals. Protein depletion in SS compared with C animals was evident for heart, pancreas, and intestinal mucosa. Unless aggressively supplemented, low-calorie SS diets may deplete protein stores of the gastrointestinal organs of digestion and absorption and contribute to decrease in body nitrogen stores, specifically cardiac muscle.