In our previous studies on the relationship between prolonged physical stress and muscle enzyme activities, a number of individuals suffered a hyponatremic state. The present study was conducted to evaluate the effect of prolonged physical stress on the development of hyponatremia. Seventeen physically fit male subjects were studied during a 24-hour endurance march. Serum sodium, that averaged 142 +/- 2 before the march, decreased during the march to 135 +/- 2 mEq/l (p less than 0.01 versus before the march). Blood and plasma volumes increased by 8 and 16% (p less than 0.05), respectively. Creatinine clearance before the march declined from 118 +/- 24 to 74 +/- 19 ml/min (p less than 0.005) during the march and correlated negatively with serum sodium (p less than 0.002; r = 0.59). Urinary sodium excretion before the march was 132 +/- 55 and during the march was 123 +/- 62 mEq/24 h. Free water clearance rose during the march and correlated negatively with serum sodium (p less than 0.001), suggesting an appropriate renal diluting response. However, the fall in serum sodium correlated positively with water intake (p less than 0.01; r = 0.59). These results show that hyponatremia develops during endurance marching in normal subjects on an unrestricted high water intake. The renal response to water intake is appropriate; however, the subjects fall to produce maximally diluted urine. Therefore, we suggest that water intake should follow physiological needs and not forced to cause hyponatremia during prolonged physical stress.