Infections caused by Escherichia coli have an economically significant impact on the poultry industry and a non-serotype-specific vaccine appears to be the most logical method of controlling them. The core oligosaccharide-lipid A region of bacterial lipopolysaccharide (LPS) is well conserved and highly immunogenic but toxic. This study determined the possible use of a liposome-encapsulated mixture of rough LPSs of core types R1, R2, R3 and R4 in controlling infections caused by E. coli in chickens. The liposome which encapsulated the LPS consisted of egg phosphatidylcholine, bovine brain phosphatidylserine and cholesterol. As determined by Limulus amoebocyte lysate assay, incorporation of LPS into the liposome reduced the endotoxicity of LPS to 0.7 % of its initial value. When tested on a chicken macrophage cell line (HD11), liposome-incorporated LPS produced a significantly lower amount of nitric oxide (<5 microM) than that produced by free LPS (22 microM). Transcription of the genes for interleukin-1beta and inducible nitric oxide synthase was lower in cells treated with liposome-incorporated LPS than in cells treated with free LPS. When chickens were immunized with 0.2 microg, 1 microg and 5 microg liposome-encapsulated mixture of LPS core types, the antibody response increased with increasing dose. When challenged with the virulent E. coli O78 strain, the birds which received 1 microg liposome-encapsulated LPS and 5 microg LPS had significantly lower lesions scores (P <0.05) and high body weight when compared with the birds in the control group as well as with the birds immunized with a suboptimal dose (0.2 microg) of liposome-encapsulated LPS.