Since a complete coverage of quaternary folding space still needs a long period of time, a highly selective determination of unique protein complex structures is essential to speed up the process. Expanding knowledge and understanding of the substantial role of phages in the biosphere, as well as the potential of phage medical applications, renewed the interest of the Western scientific community in phages. R428 Practical applications of bacteriophages as antibacterial agents or for potential correction of the composition of natural body-associated bacterial communities will require defined pharmacokinetic parameters and identification of the mechanisms of immunobiological activities demonstrated for some bacteriophages. The interactions of bacteriophages with human and animal organisms depend on the rate of the elimination of the phages by the immune system. Wild type bacteriophages are rapidly sequestered in the spleen and liver and then degraded by macrophages and other mechanisms. The time of the circulation of bacteriophages in blood can be significantly changed by modifications in the surface proteins of the viral particles. The interaction of the bacteriophage particles with immune system cells was recently shown to mediate non-bactericidal biological activities of the phage preparations. Bacteriophage T4 and some of its mutants were shown to exert various effects on mammalian cells and immunity both in vivo and in vitro. Investigation of the exact molecular mechanisms of observed phage immunobiological activities requires experimental study of the interaction of surface-exposed individual viral proteins with immune cells and receptor molecules. A wide choice of expression systems exists nowadays, allowing one to produce almost any recombinant proteins in a variety of conditions. The simplest and cheapest heterologous bacterial expression systems are based on E. coli, a natural host for T4 bacteriophage. Other bacterial products, e.g. bacterial DNA and peptidoglycan. The immune system is highly sensitive to stimulation by microbial-derived substances. Particularly LPS is a potent activator of many physiological processes in animals, both regular and pathological ones, in vivo and in vitro. Presence of LPS and other immunogenic bacterial components may strongly interfere with investigation of protein activities. Here we present an optimized method for production of gp23, gp24, gphoc and gpsoc proteins, forming the outer surface of the T4 phage head. The lattice of the T4 head is made of 930 Major Capsid Proteins that form 155 hexamers. The centre of each hexamer is occupied by Highly Immunogenic Outer Capsid Protein, i.e. 155 molecules per capsid. The gphoc molecule extends about 6 nm away from the head surface. Gphoc has the shape of a dumbbell with a globular head, a neck, and a base that binds to the gp23 hexamers. Eleven head verticles are occupied by pentamers of Head Vertex Protein, and the twelfth is connected to the tail. Between gp23 hexamers, a planar mesh of Small Outer Capsid Protein is incorporated.