Although the activating factor FA of the type-1 protein phosphatase has long been recognized as a cytosolic enzyme involved in the regulation of cell metabolism and nervous functions, strong indications have been obtained that FA is in fact a membrane-bound protein kinase in most mammalian tissues. For instance, direct treatment of the tissue extracts including brain, liver, cardiac, smooth and skeletal muscles with 1% Triton X-100 can cause several fold stimulation of the FA activity. Moreover, at least 50% of the FA can be detected in the particulate fractions of the extracts. Chromatography of the extracts in the presence and absence of Triton X-100 further demonstrate these results. The data can now explain the reason why most people can not isolate reasonable amount of FA from mammalian tissues. It is recommended that Triton X-100 should be used for purification of FA from most mammalian tissue extracts. The results also suggest that most previous studies on the action of FA involved in the regulation of cell functions should be re-evaluated and the membrane-associated FA should be taken into consideration.