The cell envelope of Escherichia coli is usually described as a 3-layered structure. The outermost layer, the outer membrane, is composed primarily of phospholipids, lipopolysaccharide and proteins. The proteins are distinquished in that a few (4-6) major proteins with molecular weights between 7,800 and 40,000 account for about 70% of the total protein found in the outer membrane. Our goal is to describe the means whereby the major outer membrane proteins are synthesized and translocated specifically to this membrane and to define their physiological function. We have isolated mutants missing as many as 4 of these major outer membrane proteins by selection of colicin-tolerant and/or bacteriophage-resistant cells. For example, outer membrane materials prepared from to1F mutants lack a specific major outer membrane protein, protein Ia. The loss of this protein is almost completely compensated for by the increased levels of one or two other major outer membrane proteins. Analysis of mutants missing protein Ia has revealed there are several genetic loci (at least 4) concerned with the expression of outer membrane protein Ia. Studies of these loci should provide information on the regulation of synthesis of protein Ia. BIBLIOGRAPHIC REFERENCES: Foulds, J.: to1F locus in Escherichia coli: Chromosomal location and relationship to loci cm1B and to1D. J. Bacteriol. 126: 604-608, 1976. Chai, T. and Foulds, J.: Escherichia coli K-12 to1F mutants: Alterations in protein composition of the outer membrane. J. Bacteriol. 130: 781-786, 1977.