A beta-galactoside-specific lectin from proprietary mistletoe extract, recently reported to exhibit immunomodulatory potency in vivo (T. Hajto, K. Hostanska, and H J. Gabius, Cancer Res. 49: 4803-4808, 1989), induced increased secretion of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in cultures of human peripheral blood mononuclear cells. The enhancement of secretion, determined independently by bioassays and enzyme-linked immunosorbent assay-based quantitation, was caused by selective protein-carbohydrate interaction, as revealed by the strict dependence on the presence of the carbohydrate-binding subunit of the specific lectin-binding sugar as well as anti-lectin antibodies. Increased cytokine levels in serum of patients after injection of optimal lectin doses corroborated the in vitro results. Thus, these data provide an explanation for the increases in cellular parameters of the host defense system in vivo, which presents a further step toward their potentially beneficial clinical exploitation in standardized regimens.