Intense muscle contractions result in large changes in the intracellular concentrations of electrolytes. The purpose of this study was to examine the contributions of changes in intracellular strong ions to calculated changes in steady-state membrane potential (Em) and muscle intracellular H+ concentration ([H+]i). A physicochemical model is used to examine the origin of the changes in [H+]i during intense muscle contraction. The study used the isolated perfused rat hindlimb intermittently stimulated to contract at high intensity for 5 min. This resulted in significant K+ depletion of both slow (soleus) and fast (white gastrocnemius, WG) muscle fibers and a release of K+ and lactate (Lac−) into venous perfusate. The major contributor to a 12- to 14-mV depolarization of Em in soleus and WG was the decrease in intracellular K+ concentration ([K+]i). The major independent contributors to [H+]i are changes in the concentrations of strong and weak ions and in CO2. Significant decreases in the strong ion difference ([SID]i) in both soleus and WG contributed substantially to the increase in [H+]i during stimulation. In WG the model showed that the decrease in [SID]i accounted for 35% of the increase in [H+]i (133–312 nequiv/L; pHi = 6.88–6.51) at the end of stimulation. Of the main contributors to decreased [SID]i increased [Lac−]i and decreased [K+]i contributed 40 and 60%, respectively, to increased [H+]i whereas a decrease in [PCr2−]i contributed to reduced [H+]i. It is concluded that decreased muscle [K+], during intense contractions is the single most important contributor to reduced Em and increased [H+]i. Depletion of PCr2− simultaneous to the changes in [Lac−]i and [K+]i prevents larger increases in [H+]i and helps maintain the intracellular acid–base state.Key words: exercise, acid–base, membrane potential, potassium, lactate.