The protective and toxic properties of a ribosomal vaccine prepared from Salmonella typhimurium W118-2 were systematicaly compared with those of an acetone-killed whole cell vaccine, purified lipopolysaccharide, and living cells in CD-1 mice. Tests of graded immunizing doses of each vaccine against several challenge doses of live strain W118-2 showed that, although the protection given by ribosomes approached the levels of protection conferred by living organisms, acetone-killed cells administered in appropriate dosages provided levels of protection comparable to that of ribosomes. Lipopolysaccharide was found to be significantly less protective than the other vaccines. On a dry-weight basis, ribosomes were the least toxic with a 50% toxic dose (TD50) of 5,000 microgram; acetone-killed cells had an intermediate TD50 of 1,400 microgram; and lipolysaccharide was the most toxic, with a TD50 of 320 microgram. The dose of each vaccine that protected 50% of the mice against a challenge of 1,00 times the 50% lethal dose was determined and divided by the TD50 to give the therapeutic index. This ratio also indicated that the ribosomes and acetone-killed cells were equally effective, whereas lipopolysaccharide was markedly inferior.