Dichloroacetate (DCA), a stimulator of the pyruvate dehydrogenase complex, decreases lactate levels and peripheral resistance and increases cardiac output. This study was performed to examine the effects of DCA on exercise performance in humans. Eight healthy male volunteers (age 20-28 years) were tested by bicycle spiro-ergometry using a microprocessor-controlled gas analysis system after infusion of DCA (50 mg/kg body weight) or saline. Prior infusion of DCA significantly reduced the increase of lactate levels during exercise when compared with infusion of saline (1.40 +/- 0.21 vs 2.10 +/- 0.09 mmol.l-1 at 50% of the expected maximal working capacity, P < 0.05; 8.53 +/- 0.45 vs 9.92 +/- 0.59 mmol.l-1 at maximal working capacity, P < 0.05). Oxygen uptake increased significantly after DCA when compared with saline from 7.5 +/- 0.4 vs 7.4 +/- 0.5 to 27.2 +/- 1.5 vs 23.7 +/- 1.7 (P < 0.05) at anaerobic threshold and to 35.6 +/- 1.7 vs 30.5 +/- 1.0 ml.kg-1 min-1 (P < 0.05) at maximal exercise capacity. Following DCA infusion the workload at which the anaerobic threshold was reached was significantly higher (160 +/- 7 vs 120 +/- 5 W, P < 0.05) and the maximal working capacity was significantly increased (230 +/- 9 vs 209 +/- 8 W, P < 0.05). In summary, DCA reduced the increase of lactate levels during exercise and increased oxygen uptake at the anaerobic threshold and at maximal working capacity, which was significantly increased. These results warrant further studies on a potential therapeutic application of DCA in patients with reduced exercise capacity.