Context: Sodium replacement during prolonged exercise in the heat may be critically important to maintaining fluid and electrolyte balance and muscle contractility.Objective: To examine the effectiveness of sodium-containing sports drinks in preventing hyponatremia and muscle cramping during prolonged exercise in the heat.Design: Randomized crossover study.Patients or Other Participants: Thirteen active men. Intervention(s): Participants completed 4 trials of an exercise protocol in the heat (306C) consisting of 3 hours of exercise (alternating 30 minutes of walking and cycling at a heart rate of 130 and 140 beats per minute, respectively); a set of standing calf raises (8 sets of 30 repetitions); and 45 minutes of steep, brisk walking (5.5 km?h 21 on a 12% grade). During exercise, participants consumed fluids to match body mass loss. A different drink was consumed for each trial: carbohydrateelectrolyte drink containing 36.2 mmol/L sodium (HNa), carbohydrate-electrolyte drink containing 19.9 mmol/L sodium (LNa), mineral water (W), and colored and flavored distilled water (PL).Main Outcome Measure(s): Serum sodium, plasma osmolality, plasma volume changes, and muscle cramping frequency.Results: During both HNa and LNa trials, serum sodium remained relatively constant (serum sodium concentration at the end of the protocol was 137.3 mmol/L and 136.7 mmol/L, respectively). However, a clear decrease was observed in W (134.5 6 0.8 mmol/L) and PL (134.4 6 0.8 mmol/L) trials compared with HNa and LNa trials (P , .05). The same trends were observed for plasma osmolality (P , .05). Albeit not significant, plasma volume was preserved during the HNa and LNa trials, but a reduction of 2.5% was observed in the W and PL trials. None of the volunteers experienced cramping.Conclusions: The data suggest that sodium intake during prolonged exercise in the heat plays a significant role in preventing sodium losses that may lead to hyponatremia when fluid intake matches sweat losses.Key Words: endurance, fluid replacement, hydration, hyponatremia, plasma volume, sports drinks Key Points: N Under environmental conditions in which fluid intake matched body mass loss, relatively moderate amounts of sodium added to the hydration solution attenuated the decline in sodium concentration of plasma and preserved plasma volume at pre-exercise levels.N Sodium supplementation did not increase serum sodium even when participants consumed a carbohydrate-electrolyte drink containing 36.2 mmol/L sodium.N A relationship between sodium supplementation and the prevention of exercise-associated muscle cramps cannot be established from the environmental and exercise factors of this study.N Further research using appropriate exercise protocols is needed to clarify the effect of sodium supplementation on the propensity to cramp during exercise.