Objective: The present study was undertaken to investigate the ventilatory response due to sustained isocapnic moderate hypoxia and the possible role of adenosine in hypoxic depression in anesthetized cats. Materials and Methods: Cats anesthetized with pentothal sodium (30 mg kg(-1) i.p.) were divided into two groups: treated (n=11) and control (n=15). Respiratory frequency (f), tidal volume (V-T), minute volume ((V)over dotE) and systemic arterial blood pressure were recorded during air and 20 min of breathing hypoxic gas mixture (14% O-2-86% N-2). Isocapnia was maintained by adding fractions of 1% CO2 to the inspired hypoxic gas mixture. The PaO2 and PaCO2 were determined. Results: On hypoxic gas mixture breathing, V-T and (V)over dotE values of the control animals increased significantly, at 5 min to 50+/-6 and 53+/-6%, respectively, above the prehypoxic air phase value (p<0.001). After that, the magnitude of increase in V-T and (V)over dotE declined gradually. At 20 min of hypoxia, V-T and (V)over dotE were less than those in prehypoxic air phase (17 +/- 7, 16 +/- 7%, respectively). In cats injected with an adenosine antagonist (theophylline 13.6 mg kg(-1) i.v.), f, V-T and (V)over dotE increased significantly at 5 min of hypoxia (p<0.001). At 20 min of hypoxia, f, V-T and (V)over dotE were 8+/-2, 30+/-8, and 39+/-8%, respectively, higher than corresponding values of the prehypoxic stage. In cats injected with theophylline (0.5 mg kg(-1)) by cisternal puncture V-T and (V)over dotE increased significantly at 5 min of hypoxia. At 20 min of hypoxia, V-T and (V)over dotE were 27+/-7 and 31+/-8% higher than those in the prehypoxic air phase. Conclusion: The results of this study show that accumulation of adenosine in the brain during hypoxia seems to reduce the response of the central mechanisms to chemoreceptor impulses. Copyright (C) 2004 S. Karger AG, Basel.