Histamine induces the T-cell dependent production of both suppressive and enhancing factor via its interaction with H2-receptors. This could be shown by the transfer of cells or crude lymphokine preparations after in vitro histamine treatment into recipient mice, which were characterized with respect to their humoral immune response. The effective histamine concentrations differed remarkably among different mouse strains which indicates a complex regulatory network. The combined in vitro/in vivo approach as performed in these experiments leads to the conclusion that histamine may act as a suppressive as well as an enhancing immunomodulator on the humoral immune response in vivo.