Histaminergic neuron cells send fiber terminals to almost all parts of the brain, and the histamine receptors on astrocytes are the main targets of central histaminergic neurons. But no proof of the significance of histamine and its specific receptors on human malignant astrocytoma cells has been presented to date. Our results show that six malignant glioma cell lines used in this experiment secreted histamine into the culture medium and that the histamine stimulated their DNA synthesis in a dose-dependent manner. Moreover, histamine induced accumulation of inositol triphosphate (IP3) in all cell lines in either a time- or a dose-dependent manner, whereas cAMP accumulation was not induced by it in any of these cell lines, indicating that these cell lines express the H-1-receptors but not the H-2-receptors. In vivo, thus, malignant glioma may possibly produce histamine, which then would stimulate their neoplastic behavior mediated by the H-1-receptor.