The phospholipases are a diverse group of enzymes, produced by a variety of Gram-positive and Gram-negative bacteria. The roles of these enzymes in the pathogenesis of infectious disease is equally diverse. It is only recently that molecular genetic approaches have allowed data to be obtained which indicates the role of these enzymes in the disease process. In the case of some pathogens phospholipases play an overriding role in disease. Roles for these enzymes have been demonstrated in the pathogenesis of disease caused by extracellular and intracellular pathogens and by disease caused by pathogens which enter via the respiratory tract, the intestinal tract or after traumatic injury. Some of the mechanisms by which phospholipases C affect tissues in vitro or ex vivo are understood but, in the main, the mechanisms by which phospholipases C affect tissues in vivo are not known. A key event, which can determine the extent of involvement of phospholipases in the disease process, is the interaction of the enzyme with phospholipids in eukaryotic cell membranes. Whilst progress has been made in understanding the molecular basis of these interactions, the process is far from understood. Two theories attempt to explain the reasons why only some phospholipases C are membrane active. In general, the membrane active enzymes are able to hydrolyse both phosphatidylcholine and sphingomyelin and appear to have mechanisms which allow them to interact with membrane phospholipids. The structural differences between phosphatidylcholine and sphingomyelin lie within the fatty acyl chain/ester bond region which would be partially embedded in the membrane bilayer. Therefore, there may be a common explanation for membrane interaction and recognition of both phospholipid types. The value of this information will be several fold. The demonstration of the role of these enzymes in disease will allow the development of vaccines or therapeutics which block the effects of these enzymes. In this context it is worth bearing in mind that eukaryotic phospholipases C, which play key roles in many inflammatory and autoimmune diseases, are the subject of intense study by the pharmaceutical industry. Some of the bacterial toxins are potent cytotoxic agents and this has encouraged some workers to explore the possibility that immunotoxins can be developed (Chovnick et al. 1991). Purified recombinant phospholipases C will continue to be used in the study of cell membranes, and the increasing numbers of enzymes with different substrate specificities will enhance their application.