Gas exchange and the correlated changes in blood and tissue metabolic and acid-base status were investigated during long term exposure of the toad Bufo marinus to graded levels of hypoxia. During hypoxia, PCO2 values in blood and tissues fell, leading to a transient alkalosis in the extracellular but not in the intracellular space. A reduction in blood perfusion of the skin during hypoxia may explain why PCO2 was low in sartorius muscle under normoxia, but approached the PCO2 values found in other tissues (gastrocnemius muscle, ventricle) under hypoxia. At PO2 values below the critical PO2, lactate was formed and the decrease in total CO2 was accelerated. Lactate levels in the plasma were higher than in the intracellular space of the skeletal muscles, a finding attributed to the pH-dependent distribution of lactic acid across the cell membrane. The comparison of metabolic proton quantities with those found in the extra- and intracellular acid-base status suggests that CO2 release was accelerated by anaerobic proton formation. The alkalizing effect of decreasing PCO2 in the skeletal musculature was compensated for by a release of base equivalents into the blood. The resulting alkalosis in the blood was probably compensated for by the release of base equivalents into the environment. © 1991.