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The objective of this study was to test the hypothesis that the incidence and severity of clinical coliform mastitis could be decreased by Re-17 mutant Salmonella typhimurium bacterin toxoid. Holstein-Friesian cows from two Arizona dairies were selected for this study based on July through November projected calving dates; peak lactation occurred during the period of highest rainfall and peak environmental stress. The cows were randomly assigned to either a vaccinate or a control group, and 1292 cows were paired by herd, parity, calving date, and milk yield. The 646 vaccinates were injected twice during the third trimester of pregnancy with an Re-17 mutant S. typhimurium bacterin toxoid, and the 646 controls were not vaccinated. Vaccinated cows had significantly fewer clinical cases of coliform mastitis with positive coliform cultures and had lower culling rate from coliform mastitis than control cows during the first 5 mo of lactation. During the same period, the mortality rate from clinical coliform mastitis was 75% less in the vaccinated clinical coliform mastitic group than in the control group. Incidence of mastitis increased with advancing parity. The Re-17 mutant Salmonella typhimurium bacterin toxoid provided cross-protection against coliform mastitis; incidence and severity of clinical coliform mastitis were significantly lowered during the first 5 mo of lactation.