The effects of hypoxia on acid-base balance and blood gases were examined in larval Ambystoma tigrinum. Environmental hypoxia (Po7 = 24 mm Hg) resulted in a severe metabolic acidosis. During approximately 4 hr of hypoxia, arterial Po, fell from 23 to 8 mm Hg while Pcoz did not change; plasma lactate concentrations rose from 1.7 to 11 mM; pH fell from 7.9 to 7.3 and [HC03-l decreased by 8.2 mM. After restoration of normoxia, Po, rose to 40 mm Hg within 1 hr. All variables returned to control levels between 4 and 24 hr. Circulating levels of norepinephrine were significantly increased and highly correlated with pH after 4 hr of hypoxia. Net and unidirectional Na' and C1-flux rates were measured before, during, and after hypoxia to determine if cutaneous ion exchange is associated with the acid-base disturbance. Neither Na' nor C1-flux rates changed significantly during hypoxic exposure or recovery.