1. The addition of adenosine, CO2 and lactate to the venous blood draining an isolated constant-flow perfused gracilis muscle was studied in anaesthetized and artificially ventilated dogs during twitch and tetanic contractions. 2. Venous adenosine concentration increased from 154 +/- 33 nM (mean +/- S.E.M.) to 279 +/- 121 or 280 +/- 125 nM after 10 min of 1.5 or 3 Hz twitch contractions and to 240 +/- 120 or 276 +/- 139 nM after 10 min of 1 or 5 s tetani occurring at 0.1 Hz. Twitch contractions at 0.1 or 0.5 Hz for 10 min did not significantly elevate venous adenosine. 3. Venous lactate concentration was significantly increased after 10 min of 1.5 or 3 Hz twitches or 5 s tetani at 0.1 Hz. There was a good correlation (r = 0.70; P < 0.001) between venous adenosine and lactate concentrations. 4. Venous partial pressure of CO2 (PCO2) was significantly elevated after 10 min of 1.5 or 3 Hz twitch contractions or 1 or 5 s tetani at 0.1 Hz. There was also a good correlation (r = 0.58; P < 0.001) between venous adenosine concentration and PCO2. 5. Venous partial pressure of O2 (PO2) decreased during all contractions except those at 0.1 Hz, but the oxygen cost per unit of tension x time was similar during every pattern of stimulation, and the percentage of the total energy production achieved by anaerobic means during muscle contractions did not exceed that at rest, indicating that there had been no limitation to the oxygen supply. Venous PO2 was poorly correlated with venous adenosine concentration (r = 0.28), but quite well correlated with venous lactate concentration (r = 0.53; P < 0.001). If the indirect influence of PO2 on venous adenosine concentration via an increase in lactate concentration was eliminated by partial correlation, then the coefficient for the relationship between venous adenosine concentration and venous PO2 became 0.15. 6. There was a significant correlation between the venous adenosine concentration and the venous pH (r = 0.53; P < 0.001). If the influence of oxygenation on venous adenosine and pH was eliminated by partial correlation, the coefficient for the relationship between venous adenosine and pH increased to 0.95.(ABSTRACT TRUNCATED AT 400 WORDS)