Three-wk-old genetically lean or obese pigs were used in two experiments to determine the changes in body composition, visceral organs and brain in response to severe protein deficiency. In Experiment 1, 16 obese pigs were fed an adequate (A, 21% protein, 3% fat) or a protein-deficient (D, 5% protein, 23% fat) diet for 7 wk. One-half of each group was killed at 7 wk, and the remainder of each group was fed the A diet for an additional 8 wk. At 7 wk, pigs fed D contained a higher percentage of fat than those fed A (P < 0.01); after 8-wk of repletion, body composition of the two groups was similar. Duodenum, jejunum, and ileum of the protein-deficient pigs had severely atrophic villi, submucosal edema, and atrophic muscle layers; after 8 wk of repletion, however, microscopic architecture of the gastrointestinal tract was restored to normal. Absolute cerebrum weight at 7 wk, but not after 8 wk repletion, in the pigs fed D were significantly less than in pigs fed A, indicating reduced brain cellularity after 7 wk of protein restriction, but not after 8 wk repletion. In Experiment 2, genetically obese (O, n = 8) and lean (L, n = 8) pigs consumed the A or D diet ad libitum for 10 wk. L and O pigs responded similarly to protein deficiency; D pigs were fatter than A pigs and plasma constituents, bone mineral content, bone mineral density and most organ weights revealed no interactions between diet and genotype. The pig model system used in these experiments enabled the isolation of protein deficiency from infectious disease, parasites and social environmental stimulation that may confound interpretation of human infant malnutrition experiments. The data suggest that genetically controlled body fatness is not a major determinant in the response of the infant pig to severe protein deficiency.