SAA has been shown previously to inhibit the in vitro antibody response of normal murine spleen cells to SRBC. This effect is nonspecific but does not directly suppress B cells. To evaluate the mechanisms of this suppression, the in vitro antibody response to SRBC was studied using cells from cytoxan-treated mice. No evidence for preformed suppressor cells was found. Also, preincubation of normal cells with SAA failed to reveal evidence for the generation of suppressor cells in vitro. The addition of 2-mercaptoethanol to cultures completely reversed the suppression caused by SAA. Addition of either normal T cells or normal macrophages to cultures partially reversed suppression caused by SAA, but only a combination of T cells and macrophages could completely reverse the suppression. These data are consistent with an effect of SAA on macrophage-T cell interaction in the generation of the immune response to T-dependent antigen. No evidence for the participation of suppressor cells as has been demonstrated for alpha-fetoprotein was found.