The response to IL-2 and IL-4 of several functionally defined lymphoid cell types was assessed at the individual responding cell level in limiting dilution experiments in which exogenous IL-2 or IL-4 was used to promote cellular activation and expansion. Splenic precursors that give rise to alloreactive CTL in LDA supplemented with IL-2 were approximately 3-fold more frequent than those detected in IL-4. Of special interest was the observation that cytolytic cultures arising in primary allogeneic LDA supplemented with IL-4 exhibited a greater degree of lytic specificity than those arising in IL-2. This difference may be due to an inherently broader specificity of CTL cultured in IL-2 or to a concomitant activation of CTL and lymphokine-activated killer(s) (LAK) in individual IL-2 supplemented microcultures. In this regard, estimation of LAK precursor(s) (LAK-P) frequencies in LDA cultures established without an overt antigenic stimulus revealed that IL-2 activates a 20-fold higher frequency of LAK-P than does IL-4. Finally, an examination of the proliferative response to IL-2 and IL-4 of several CTL and PTL clones demonstrated that IL-4 responsive cells comprise a subset of cells that respond to IL-2, irrespective of their functional phenotype.