In late summer, semipalmated sandpipers (Calidris pusilla) migrate nonstop from eastern Canada to wintering sites on the northwest coast of South America. Before their transoceanic flight, the birds feed intensively for about 15 days during which time lipids are stored. The fat-free dry mass of the pectoralis muscle increases during the fattening period, probably increasing the maximal power output of the muscle. Plasma free fatty acids and triglycerides, pectoralis muscle lipid content, and the activity of carnitine oleoyl coenzyme A transferase are higher in heavy (fat) than in light (lean) birds. These alterations imply an enhanced capacity to utilize fatty acids as a metabolic fuel during migration. Total pectoralis muscle glycogen levels and the activity of pyruvate kinase increase, suggesting a higher capacity for glycogenolysis, which may be important during intense levels of energy demand. Heart size and protein content per gram of tissue increase in association with an increase in body mass. However, total levels of key mitochondrial enzymes, citrate synthase and carnitine oleoyl coenzyme A transferase, do not change, suggesting that in the heart an increase in total protein content occurs without an increase in mitochondrial proteins.