We speculated that frusemide would attenuate the acidosis associated with intense exertion, and that weight carriage would mitigate this effect. Therefore, in each of 2 experiments we measured pulmonary artery and systemic arterial blood pH, Pco2, Po2 and pulmonary artery temperature in 9 horses during exertion on a treadmill after each of 3 treatments. The treatments were: 1) injection of saline solution (C), 2) injection of frusemide (1 mg/kg bwt, i.v. 4 h before running) (FU) and 3) injection of frusemide (F) as for FU and the horses carried weight equal to that lost in the 4 h after frusemide administration (FL). In Experiment 1 the horses performed an incremental exercise test of 90 s at each of 4, 7 and 9 m/s (4° incline). In Experiment 2, the horses ran on a treadmill inclined at 4° for 3 min at 3 m/s, at approximately 120% V̇o2max for 2 min, and 3 m/s for 5 min. Blood samples for measurement of blood pH, Pco2 and Po2 were collected into heparinised glass syringes. Values were adjusted for changes in pulmonary artery blood temperature. Data were analysed using a 2 way repeated measures ANOVA. There was a consistent pattern in both experiments characterised by a mild alkalosis or mitigated acidosis, compared to C, at rest and during exercise and recovery after FU (P<.05). Weight carriage blunted or inhibited the effect of frusemide during exercise and recovery. In experiment 2, at the end of the sprint, FU treatment resulted in a less severe acidosis than did C or FL: mixed venous pH for C, FU, and FL at the end of the sprint were 6.93, 6.98 and 6.93, respectively (P interaction=0.038), mixed venous base excess was -12.4, -9.91, and -11.8 mmol/l, respectively, and arterial base excess of -14.4, -12.7 and -14.1 mmol/l (P interaction = 0.006) respectively. These effects persisted into recovery. A similar pattern of responses occurred during the incremental exercise test, with weight carriage offsetting the alkalinising effect of frusemide. We conclude that frusemide attenuates the acidosis of intense exertion and that carriage of weight prevents this effect.