The present study examined K+ fluxes in red blood cells and muscle during muscle contractions. Seven subjects performed two-legged submaximal knee-extensor exercise for 30 min. After 10 min of leg exercise (L1), intense arm exercise was also performed for 10 min (L2+A). Plasma epinephrine and norepinephrine concentrations were higher (P < 0.05) in L2+A compared with L1. Arterial plasma K+ at the end of L2+A was higher than in L1 (5.6 vs. 4.4 mM, P < 0.05) and returned to the L1 level on cessation of arm exercise. A net K+ release of 0.16 mmol/min from the active legs during L1 was turned to a net K+ uptake of 0.79 mmol/min during L2+A. Both arterial and venous red blood cell K+-to-hemoglobin ratios were constant during exercise. The present data suggest that contracting muscle can take up K+ probably by a combination of K+ and hormone activation of the Na+-K+ pump. Furthermore, changes in red blood cell K+ concentrations during muscle activity appear to be due to water movements and not transmembrane fluxes of K+.