Examples of our work concerning the production, action, and genetic control of response to interferon are reviewed. We have shown that human immune interferon is a product of mitogen stimulated T lymphocyte subsets T mu, T gamma, and T phi, and have investigated some of interferon's antiviral, antiproliferative, and antidifferentiational (or antimaturational) effects. We also have refined the genetic locus that controls response to interferon to the distal segment of the long arm of chromosome 21 in the human, and have mapped it for the first time to chromosome 16 in the mouse. We have demonstrated that imbalance of this locus in the human, as in trisomy 21, results in enhanced sensitivity of cells to interferon which, because of its immunoregulatory effects, may be involved in the abnormalities of the immune response in such patients.