Animals subjected to hypoxia become hypocapnic and after some hours show an increase in circulating erythropoietin. The steps involved in the increased production of erythropoietin in response to hypoxia are not fully understood, although it has been postulated that changes in coincident variables such as acid-base balance may contribute to the mechanism of increased erythropoietin production. A rabbit model has been used to determine the physiological changes which occur in short-term hypobaric hypoxia. After 1 h, no changes were found in pCO2, pH, P50, base excess, standard bicarbonate or serum erythropoietic activity (SEA). After 3 h the pCO2, pH, base excess and standard bicarbonate had decreased while the P50 and SEA had increased. After 6 h, although the pCO2 was still significantly reduced, the pH, base excess and standard bicarbonate had returned to the initial levels and maximal SEA values. 20-fold greater than the pre-hypoxia values were found. Overall the data are consistent with the view that the magnitude of the erythropoietic response to hypoxia is modified by changes in acid-base balance.