The capacity of retinoids to amplify the proliferative response of BALB/c lymphocytes to concanavalin A (Con A)2 in the presence of exogenous interleukin-2 (IL-2) and the induction of IL-2 receptors (IL-2R) on L3T4+ and Lyt-2+ T-cells was evaluated. Preincubation with Con A for 8 h in the presence of retinoids resulted in a greater than two-fold increase in spleen cell proliferative response to Con A plus rIL-2 over the following 72 h relative to the response of cells preincubated with Con A alone. Peak potentiation of IL-2 responses occurred over a pharmacologic range of retinoic acid (RA) concentration (10(-10)-10(-8) M) in the presence of 20 U/ml rIL-2. This potentiation of the response to IL-2 was likewise observed after 8 h prestimulation with Con A with splenic T-cells enriched by passage over nylon wool. Preincubation of the spleen cells with Con A plus RA without the subsequent addition of IL-2 resulted in a proliferative response that was potentiated nearly to the level of the response produced by subsequent addition of IL-2 to Con A-activated cells. Preincubation of the cells with Con A in the presence of RA produced a true synergy with IL-2; the resulting increase in response was greater than the sum of the increases produced by RA or IL-2 alone.(ABSTRACT TRUNCATED AT 250 WORDS)