An enhancing effect of histamine on the biosynthesis and gene expression of interleukin-6 (IL-6) by human cell lines, Epstein-Barr virus (EBV)-infected human B lymphoma line BMNH and the glioblastoma line SK-MG4 has been found. No similar effect of histamine has been detected on the IL-6 production by any other B-cell line, CESS or human peripheral monocytes. Histamine stimulates the IgM production of BMNH cells by autocrine action of IL-6 induced by histamine, since either neutralization of IL-6 by polyclonal antibody or blocking the IL-6 receptor by specific monoclonal antibody abolished the effect of histamine.