SUMMARY Colostrum-deprived lambs and CF1 mice were vaccinated with water-in-oil emulsion vaccines containing nonviable whole cells (wc) of Corynebacterium pseudotuberculosis with and without muramyl dipeptide (mdp). Efficacy of vaccines was determined from the survival of mice and lesions in lambs after IV injection of 104 colony-forming units of C pseudotuberculosis. In mice, protection was related to the concentration of wc in the vaccine. At 50, 100, or 150 μg of wc, protection was good (78.8%). At 10 or 25 μg of wc, protection was considerably less (54.7%). At high wc concentrations, protection could only be moderately increased to 82.3% with high (50 and 100 μg) concentrations of mdp or increased to 90% protection with low (5 and 10 μg) concentrations of mdp. At low wc concentrations, protection significantly decreased to 32% (P < 0.025) with high concentrations of mdp, but significantly increased to 72.5% (P < 0.025) with low concen-trations of mdp. Therefore, the amount of protection with lower concentrations of wc and mdp was comparable with the amount of protection with higher concentrations of wc without mdp. In lambs, high prechallenge antibody titers (geometric mean titers from 5.1 to 5.4 by day 35) were observed after vaccination with wc. Protection and vaccination site abscesses in lambs were related to the concentration of wc and mdp. Pulmonary or vaccination site abscesses were not observed in 4 of 4 lambs vaccinated with 1 mg of wc + 50 μg of mdp.