Highly purified lymphocytes (> 99%) and monocytes (>90%) were isolated by CCE from peripheral blood of healthy donors. Blood lymphocytes were separated by this CCE into 9 subpopulations. The NK activities of these lymphocyte fractions against NK-sensitive K-562 cells and their LAK activities against NK cell-resistant target (Daudi) cells were assayed promptly or after incubation of the fractions for 4 days with or without an optimal concentration of IL-2. NK and LAK activities were measured by 4-hr 5'Cr-release assay. On the basis of their NK and LAK activities, these lymphocyte fractions were classified into 3 subpopulations of LAK precursors: one lacking both NK and LAK activities (Fr. 2). one with moderate NK activity but low LAK activity (Fr. 5), and one possessing both NK and LAK activities (Fr. 8). Addition of autologous fresh monocytes to the lymphocyte cultures re- sulted in a significant increase in induction of LAK activity in Fr. 2 and Fr. 5. This up-regulation of lymphocytes in Fr. 2 and Fr. 5 by monocytes was confirmed in parallel experiments by measuring the blastogenic response of the lymphocytes to IL-2. Depletion of lymphocytes in Fr. 8 of CD16+ (Leu-I I +) NK cells resulted in 74% reduction in LAK induction, whereas depletion of mixtures of monocytes and lymphocytes in Fr. 2 of cells reacting with CD3+ (OKT3+) antibody resulted in a 66% reduction in LAK induction. This up-regulation of LAK cell induction from LAK precursors by monocytes was confirmed using 4 lines of human lung cancer cells as targets for LAK activity. These results clearly indicate that human monocytes may cause up-regulation of the expression of IL-2411duced LAK activity in T cells and in a subpopulation of NK cells.