The membrane lipid phosphatidylinositol-3,4,5-trisphosphate (PtdInsP(3)) regulates membrane receptor signalling in many cells, including immunoreceptor signalling. Here, we review recent data that have indicated essential roles for the soluble PtdInsP(3) analogue inositol-1,3,4,5-tetrakisphosphate (InsP(4)) in T cell, B cell and neutrophil development and function. Decreased InsP(4) production in leukocytes causes immunodeficiency in mice and might contribute to inflammatory vasculitis in Kawasaki disease in humans. InsP(4)-producing kinases could therefore provide attractive drug targets for inflammatory and infectious diseases.