Dry cow therapy and a Propionibaterium acnes product were evaluated in four commercial herds with low SCC. Cows were randomly assigned within herds to treatment groups of approximately 90 cows receiving dry cow therapy, P. acnes, dry cow therapy plus P. acnes, or no treatment in a factorial arrangement. Each lactating quarter of cows that received dry cow therapy was infused via the teat duct with 300 mg of cephaprin at drying off. Cows that received P. acnes were infused intravenously with .4 mg of killed P. acnes at drying off, 7 to 10 d prepartum, and within 7 d after calving. A second prepartum injection of P. acnes immunostimulator was administered to cows that did not calve within 10 d after the first prepartum injection. Dry cow therapy enhanced bacteriological cures of IMI by Staphylococcus aureus and Corynebacterium bovis at drying off. Dry cow therapy reduced incidence of new IMI by environmental streptococci and C. bovis that originated during the dry period. Cows treated with P. acnes alone had a greater incidence of new IMI by Gram-negative bacilli originating during the dry period than did cows in the other treatment groups. Incidence of clinical mastitis at calving was greater for cows receiving no treatment than for cows receiving dry cow therapy, P. acnes, or dry cow therapy plus P. acnes.