It is well established that staphylococcal delta-haemolysin is inhibited by normal mammalian sera and forms a precipitin line on gel diffusion with normal sera. The purpose of this thesis was to quantitate inhibitory activity against delta-haemolysin and to identify the serum factor(s) involved. The inhibitory titre of normal human serum assayed using purified delta-haemolysin with cod erythrocytes as indicators of haemolysis was 1/500 - 1/1000. Fractionation of serum by ultrafiltration, gel filtration in Sephadex G-150 and Sepharose 6b and ammonium sulphate precipitation indicated that at least two components of molecular weights approximately 300,000 and > 106 were involved. When affinity chromatography was done using delta-haemolysin covalently coupled to Sepharose-4B the selective removal of g-lipoprotein from whole serum was shown by immunoelectrophoresis. High density (alpha-) and low density (beta-) lipoproteins were prepared by zonal ultracentrifugation of serum using potassium bromide density gradients and characterised by polyacrylamide gel electrophoresis, immunoelectrophoresis and gel diffusion using monospecific antisera. Both alpha- and beta-lipoproteins inhibited delta-haemolysin and gave a precipitin line on gel diffusion, while fractions which were shown by immunoelectrophoresis to be devoid of such lipoproteins were non-inhibitory. Proteolytic digestion of lipoproteins with trypsin or papain did not diminish their inhibitory activity, whereas this was diminished by pretreatment with Bacillus cereus phospholipase C. Delta-haemolysin was inhibited hy phospholipids and pretreatment with phospholipase decreased the inhibitory capacity of such phospholipids and also of a serum lipid extract. The results indicated that binding of delta-haemolysin to serum lipoproteins was via the phospholipid moiety and the implications of such an interaction in terms of in vivo activity of the haemolysin are discussed
