Basic fibroblast growth factor (b FGF) was found to be equally potent mitogen as compared to alpha-thrombin to reinitiate DNA synthesis in quiescent PC12 cells. Whereas thrombin was found to be an activator of phospholipase C as judged by a rapid increase in the formation of inositol triphosphate, inositol biphosphate and a massive accumulation of inositol phosphate when 20 mM LiCl was present as an inhibitor of inositol mono phosphatases, basic FGF failed to induce the breakdown of the polyphosphoinositides in quiescent PC12 cells to any appreciable levels, however, a simultaneous increase in the level of diacylglycerol was observed. b FGF also failed to stimulate protein kinase C which is believed to be activated by diacylglycerol. It is therefore concluded that bFGF receptor mediated 'signalling is not via phospholipase C activation and bFGF's early mitogenic responses and DNA synthesis are initiated independent of the inositol lipids and protein kinase C activation. Thus bFGF must have its own unique signal transducing mechanism independent of inositol pathways.