Mutants of Escherichia coli with altered resistance to low molecular weight organic solvents were isolated. Solvent-resistant mutants showed a decrease in the ratio of phosphatidylethanolamine to the anionic phospholipids (phosphatidylglycerol and cardiolipin) relative to the wild-type, whereas solvent-sensitive strains showed an increase. Reversion studies on representative mutants demonstrated that the phenotypic response to solvents and the changes in phospholipid composition were genetically associated. The fatty acid and lipopolysaccharide compositions of the various mutants showed no significant differences from the parental strain. The lesions in two of the solvent-sensitive mutants (DC7 and DC9) and one of the resistant mutants (DC11) were mapped by cotransduction with phage P1 and shown to lie very close to the pss locus at 56 min on the Escherichia coli map.