We studied the ventilatory and blood acid-base response of turtles to 6 h of breathing either 100% N2 (anoxic) or 95% N2-5% CO2 (anoxic-hypercapnic). In both groups, minute ventilation (VE) increased promptly with anoxia, with peak ventilation occurring between 1 and 3 h. VE then decreased but was still significantly above control at 6 h. The increase in VE resulted from increases in both respiratory frequency (f) and tidal volume (VT) but after ventilation peaked, f declined to control while VT remained elevated. We observed no significant differences in VE between the two groups in spite of significantly lower arterial pH and higher arterial PCO2 in the anoxic-hypercapnic turtles. During normoxic recovery, VE quickly increased to the peak anoxic values due primarily to a greatly increased f. In both groups, plasma [lactate-] increased during anoxia. Plasma cation concentrations also increased, partially compensating for the elevated blood lactate. We conclude that the anoxic hyperventilation did not depend on arterial pH and central chemoreceptor control but rather on peripheral hypoxic chemoreceptor control. We believe that the decline in VE during prolonged anoxic breathing results from a metabolic arrest response and/or a depression in central nervous function.