This study was undertaken to evaluate the effects of frusemide on the concentration of plasma electrolytes and the relationship between changes in electrolyte concentration and the simultaneous changes in acid-base balance in arterial and venous blood during intense exercise. Five exercise-conditioned Thoroughbred horses were exercised on a highspeed treadmill at a slope of 10% at speeds known to exceed V̇o2max. Horses participated in 3 randomised exercise trials in which they received either placebo (control), low-dose frusemide (0.5 mg/kg bwt), or high-dose frusemide (1.0 mg/kg) 4 h prior to exercise. Arterial and mixed venous blood samples were drawn before, during and after intense exercise. Packed cell volume (PCV), plasma protein, plasma electrolyte, plasma lactate concentrations and acid-base balance were determined. Frusemide at both dosages induced a significant metabolic alkalosis associated with a decrease in plasma [chloride] in both arterial and mixed venous blood. There was a highly significant correlation between the strong ion difference (SID) and [bicarbonate] in all blood samples. The effects of frusemide on electrolyte concentration and acid-base balance were largely due to changes in SID.