The relative contributions of skeletal muscle and the pulmonary bed in maintaining amino acid homeostasis were studied. Inasmuch as more than 60% of whole blood amino acid nitrogen is transported as glutamine and alanine, the flux of these two amino acids across the lungs (n = 20) and hindquarter (n = 20) was determined in the postabsorptive adult rat. Both skeletal muscle and the lungs released net amounts of glutamine and alanine in the postabsorptive state. Blood flow to the hindquarter was approximately 16% of cardiac output (3.8 +/- 0.3 cc/100 g BW/min), while pulmonary blood flow (cardiac output) was 23.7 +/- 1.7 cc/100 g BW/min. Thus, despite a lower glutamine concentration difference across the lungs (-32 +/- 6 mumol/liter) compared with the hindquarter (-59 +/- 10 mumol/liter (p less than 0.01), the lungs released significantly more glutamine (741 +/- 142 nmol/100 g BW/min) than the hindquarter (208 +/- 39 nmol/100 g BW/min) (p less than 0.01) because of the significantly higher pulmonary blood flow. Similarly, the concentration difference for alanine across the lungs was less than that of the hindquarter (-24 +/- 8 mumol/liter vs -60 +/- 12 mumol/liter, p less than 0.01) but the lungs released significantly more alanine than the hindquarter (553 +/- 159 nmol/100 g BW/min vs 221 +/- 41 nmol/100 g BW, p less than 0.01. Compositional studies demonstrated that the hindquarter comprises 40% of total body muscle mass in the rat; thus both total skeletal muscle mass and the lungs contribute approximately equally to the maintenance of blood glutamine and alanine levels.(ABSTRACT TRUNCATED AT 250 WORDS)