Phosphatidylinositol at the cytosolic leaflet of cellular membranes can be phosphorylated by a variety of kinases to produce at least seven different phosphoinositides representing all possible combinations of structures with phos phate at the 3, 4, and/or 5 positions of the inositol ring. Recent research indicates that different phosphoinositides are involved in regulating different cellular events. Activation of the p85/p110 type phosphoinositide 3-kinase (PI 3-kinase) is required for a variety of cellular responses to hormones and growth factors. This enzyme can produce PtdIns-3-P, PtdIns-3,4-P2 and PtdIns-3,4,5-P3. PI3-kinase was discovered because of its co-purification with the oncoproteins pp60v-src and polyoma middle t and was implicated in the transforming abilities of these proteins. More recently, PI 3-kinase itself was shown to be a retrovirus-encoded oncogene. To test the importance of PI 3-kinase in mammalian signal transduction pathways, a variety of techniques have been used to inhibit enzyme function, including gene knock-out. Evidence will be presented for the importance of PI 3-kinase in a variety of cellular events including cell survival, regulation of MAP kinase family members, rearrangement of actin and in come cases, regulation of cytosolic calcium. Biochemical pathways to explain these effects will be discussed.