Efflux of potassium (K+) and lactate (lac−) from active skeletal muscle during high intensity exercise leads to increased plasma [K+] and [lac−] in venous and arterial blood. The exercise-induced increases in these ions in human athletes is ameliorated, in part, by uptake by noncontracting tissue, reflected by an increase in the arteriovenous difference across these tissues from rest to exercise. To test the hypothesis that these ions are taken up by noncontracting tissue in strenuously exercising horses, plasma [K+] and [lac−] were measured in blood samples collected simultaneously from the carotid artery (CA), femoral vein (FV), and transverse facial vein (TFV) in 5 unconditioned Standardbred horses performing 4.5 min of strenuous treadmill exercise. Further, the arteriovenous differences ((a-v)diff) in [K+] and [lac−] were calculated across active tissue (CA-FV) and noncontracting tissue (CA-TFV). After 3 min of strenuous exercise, plasma [K+] in FV blood (mean ± s.e. 7.1 ± 0.2 mmol/l) was greater (P<0.05) than in CA blood (6.8 ± 0.2 mmol/l) and both of these concentrations were greater (P<0.05) than a value of 5.7 ± 0.1 mmol/l in TFV blood. Similarly, plasma [lac−] increased to 20.6 ± 0.8 and 21.1 ± 0.8 mmol/l in CA and FV blood, respectively, and these concentrations were greater (P<0.05) than a value of 19.1 ± 0.8 mmol/l in TFV blood. The magnitude of the (a-v)diff for both [K+] and [lac−] increased (P<0.05) across active and noncontracting tissue during highspeed exercise but the directions were opposite, supporting release by active tissue and uptake by noncontracting tissue. These results confirm that uptake of K+ and lac− by noncontracting tissue contributes to regulation of the plasma concentrations of these ions in strenuously exercising horses.