SUMMARYThe metabolic activity of frog lung perfused through its vascular bed has been assessed by determining changes in metabolites in the perfusion medium and by measuring the adenine nucleotides, ions and water in the tissue after perfusion under a variety of conditions. The addition of respiratory inhibitors, CN-or antimycin A, reduced the adenylate energy charge when a glucose-free perfusate was used but not when glucose was present. CN-and anaerobiosis stimulated lactate production while iodoacetate reduced lactate production and the adenylate energy charge. The addition of fatty acids, glutamine or lactate to the perfusate had no effect on the adenylate energy charge or ionic contents. With plasma albumin depleted of fatty acids in the perfusate, there was an increased production of NH4+; this could be partially suppressed by the addition of butyrate or octanoate. Glutamine increased NH4+ production and lactate was consumed by the lung, indicating that both of these substrates are metabolized. The tissue levels ofNa+ and K+ were remarkably resistant to ouabain, a concentration of 2 mmol.