The involvement of the glycosylphosphatidylinositol/inositol phosphoglycan (gly-PtdIns/IPG) system in the stimulation of macromolecular syntheses in human fibroblasts has been investigated. The study demonstrates that an insulin sensitive gly-PtdIns/IPG system is present in human fibroblasts, that IPG can significantly stimulate DNA, RNA, and protein synthesis, and that the action of insulin on DNA synthesis as well as that of IPG can be significantly reduced by a specific anti-IPG antibody. These results strongly support the hypothesis that the gly-PtdIns/IPG system is involved in the signal transduction pathway leading to the stimulation of cell proliferation.