The organization of proteins in the outer membrane of Salmonella typhimurium was analyzed by cross-linking with cleavable reagents and symmetrical two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. The major outer membrane proteins could be cross-linked to form multimeric complexes. The pore-forming 44 000, 36 000 and 34 000 dalton proteins were cross-linked to form dimers and trimers. Lipoprotein was cross-linked to 33 000 and 17 500 dalton proteins. In addition the 33 000, 24 000, 17 500 dalton proteins and the free form of lipoprotein were cross-linked to the peptidoglycan layer of the cell wall. The cross-linked complexes found were similar to those of analogous proteins in the outer membrane of Escherichia coli, thus suggesting a similar organization of outer membrane proteins in these species.