The amino acid glutamine is known to be important for the function of some immune cells in vitro. It has been proposed that the decrease in plasma glutamine concentration in relation to catabolic conditions, including prolonged, exhaustive exercise, results in a lack of glutamine for these cells and may be responsible for the transient immunodepression commonly observed after acute, exhaustive exercise. It has been unclear, however, whether the magnitude of the observed decrease in plasma glutamine concentration would be great enough to compromise the function of immune cells. In fact, intracellular glutamine concentration may not be compromised when plasma levels are decreased postexercise. In addition, a number of recent intervention studies with glutamine feeding demonstrate that, although the plasma concentration of glutamine is kept constant during and after acute, strenuous exercise, glutamine supplementation does not abolish the postexercise decrease in in vitro cellular immunity, including low lymphocyte number, impaired lymphocyte proliferation, impaired natural killer and lymphokine-activated killer cell activity, as well as low production rate and concentration of salivary IgA. It is concluded that, although the glutamine hypothesis may explain immunodepression related to other stressful conditions such as trauma and burn, plasma glutamine concentration is not likely to play a mechanistic role in exercise-induced immunodepression.