The capacity of T lymphocytes to proliferate in response to stimulation and the amount of representative lymphokines produced in vitro often correlate with the immunocompetence of patients. However, direct and indirect measurement of endogenous interferon-gamma (IFN-gamma) brings some evidence that decreased in vitro production of IFN-gamma by T lymphocytes is associated with increased concentrations in vivo. The data indicate that both a functional inhibition of IFN-gamma and its continuous presence at high levels may result in hyporesponsiveness or unresponsiveness of immune cells. A possible role of IFN-gamma in the induction of tolerance is discussed.