AbstractSeveral Ia+tumor cell lines and peritoneal exudate macrophages were tested as accessory cells (AC) for the activation of antigen‐specific T cells and for T‐B cooperation. The macrophages and all the Ia+tumor lines tested induced the release of lymphokines from T cells in a major histocompatibility complex (MHC)‐restricted fashion and reconstituted the antibody responses of AC‐depleted spleen cells or of purified T and B cells. However, only the normal macrophages but none of the tumor lines induced carrier‐specific T helper (Th) cells which help B cells for specific anti‐hapten antibody responses by linked recognition. For T‐B cooperation accessory cells were also required, but in contrast to ThCell activation any type of Ia+AC (e.g. macrophage or tumor line) was effective. Strong MHC‐restriction between the lymphocytes and the AC was seen if antigen‐pulsed AC were added into the AC‐depleted T‐B cooperation cultures. If the AC and antigen were concomitantly added to the AC‐depleted T‐B cultures, MHC‐restriction was less obvious. Concanavalin A supernatant reconstituted the response of AC‐depleted T‐B cultures provided antigen‐specific Thcells and the hapten‐carrier conjugate were present. If, however, tumor line‐activated T cells were added instead of macrophage‐induced Thcells, no cooperation with B cells took place even in the presence of Con A supernatant. The results obtained demonstrate a differential AC requirement for the induction of Thcells depending on t