Human interferon (IFN) was examined for its capacity to modify the phytohaemagglutinin (PHA)-triggered release of mitogenic factors (MF) from human lymphocytes in vitro. It was observed that the presence of partially purified leukocyte IFN (IFN-alpha) during the PHA pulsing of lymphocytes increased their subsequent release of factors which were mitogenic for fractionated T cells. A similar effect was also observed when lymphocytes were exposed to IFN-alpha prior to PHA pulsing. The possibility that substances in the IFN preparations other than IFN are responsible for the above effect is ruled out by the finding that a pure fibroblast IFN (IFN-beta) preparation also augmented the MF release by PHA-pulsed lymphocytes.