Several investigators have suggested that prolonged exercise and hypohydration alter the intravascular mass of immunoglobulins. Those studies, however, have methodological concerns which make generalizations from their data very tenuous. This study examined the effects of prolonged moderate intensity exercise in the heat and hypohydration on changes in the intravascular mass of immunoglobulins. Five heat-acclimated males attempted two Heat Stress Tests (HSTs). One HST was completed when subjects were euhydrated and the other HST when subjects were hypohydrated (-5% from base line body weight). The HSTs consisted of 30 min of rest in a 20 degrees C antechamber, followed by a 120-min exposure (2 repeats of 15 min rest and 45 min walking) in a hot (35 degrees C, 45% rh) environment. The following observations were made concerning immunoglobulin responses to hypohydration and exercise-heat stress: a) the changes in concentrations (mg.dl-1) of the measured immunoglobulins were often a reflection of changes in the plasma volume; b) hypohydration increased the intravascular mass (g) of the complement enzyme C3 during resting conditions, but did not alter the intravascular mass of IgG, IgA, and IgM, and c) prolonged treadmill exercise in the heat, when either euhydrated or hypohydrated, did not alter the intravascular mass of IgG, IgA, IgM, and C3. These data indicate that the intravascular mass of immunoglobulins does not change during prolonged moderate intensity exercise in the heat, and that hypohydration results in a translocation of C3 to the intravascular space. In addition, these data indicate that immunoglobulins do not provide a stress index for hypohydration.