The growth and differentiation of cytolytic T lymphocytes (CTL) is regulated by soluble growth hormones, of which interleukin-2 (IL-2) is considered to be of prime importance. Here we report that the lymphokine B-cell stimulatory factor (BSF-1 or interleukin-4) also has profound effects on the generation of these functionally active T cells. In particular, BSF-1 acts as a potent helper factor for the generation of CTL in primary mixed leukocyte culture (MLC) and induces cytolytic activity in in vitro primed, MLC memory populations. Direct comparison of purified recombinant BSF-1 and IL-2 reveals BSF-1 to be the more potent CTL helper factor in primary MLC. Interestingly, the two lymphokines differed in that IL-2, but not BSF-1, induced a lytic population in cultures of unprimed cells without an overt antigenic stimulus. Collectively, our data provide a direct demonstration of a heretofore undefined mechanism by which CTL activation and amplification can occur.