Variations in erythrocyte volume [mean corpuscular volume (MCV)] were evaluated during exercise and heat stress to determine the influence on calculated plasma volume and content changes. The results of this study on 17 men indicate that the human red blood cell can increase, decrease, or remain constant in volume during physical stress depending on the combined interactions of plasma osmolality and blood pH. Shrinking of MCV can occur when the increase in plasma osmolality is larger than 5 mosmol/kg H2O and the blood pH remains within 0.1 pH units of its resting value. Erythrocyte swelling is usually noticed with maximal exercise when the blood pH is less than 7.10, in spite of 20 mosmol/kg H20 increments in plasma osmolality. The regression equations indicate that during 30 min of exercise in a cool environment the plasma shifts calculated by either the hematocrit or the hematocrit + hemoglobin method fall within 1% of each other, but during resting heat exposure the hematocrit technique under-estimates the fluid shift by 2.5-3.0%. Application of these considerations to the calculation of plasma content changes during stress made it clear that the pattern of plasma potassium content is quite different with maximal as compared with submaximal exercise.