Interferons exert their antiviral, antiproliferative and immunoregulatory activities by stimulating the expression of several genes. Such genes disclose a common element within their promoters, defined Interferon Stimulated Response Element (ISRE), which binds a nuclear factor(s) translocated from the cytoplasm to the nucleus (ISGF3) after the binding of interferon (IFN) to the specific receptor. Here we report the induction of the synthesis and of the hydrolytic activity of phospholipase C gamma 1 (PLC γ1) in human T lymphocytes by IFN-β. The increased level of PLC γ1 becomes evident after 90 min of IFN-β treatment and is still detectable after 24 h. Neither the PLC γ1 overexpression induced by IFN nor the increased hydrolytic activity of the enzyme appear to be affected by pretreatment of the cells with the protein tyrosine kinase inhibitor genistein, which is known to prevent the association of ISGF3 components. These results suggest that in human T lymphocytes IFN-β can activate other transcription factor(s) distinct from ISGF3 to regulate PLC γ1 expression. In addition, the ability of this enzyme to hydrolyse PIP2, also in the presence of genistein, implies the possibility that this enzyme can exert its hydrolytic activity independently of protein tyrosine kinase activation.