This study determined the efficacy of treatment of chronic Staphylococcus aureus IMI of lactating dairy cows with a biological response modifier consisting of a killed preparation of Propionibacterium acnes. Fifty-one lactating dairy cows with chronic S. aureus IMI on two commercial dairies were enrolled in a controlled, randomized field trial. Twenty-four cows received 1 ml of the immunostimulant twice weekly for 4 wk, and the remainder of the cows served as untreated controls. Quarter milk samples were collected for SCC from all cows at 3 and 6 wk after initiation of treatment and for culture at 6 wk after initiation of treatment. If samples were negative for S. aureus at 6 wk, cows were sampled again for culture 1 wk later for 2 successive d before being considered cured. For the cows treated with immunostimulant, 16.7% (36.7% of infected quarters) were cured of S. aureus IMI; for the untreated group, 11.1% of cows (32.2% of quarters) were cured. The difference was not statistically significant. Immunostimulant treatment had no effect on quarter SCC in infected quarters overall, but, in those quarters that were cured of S. aureus infection, quarter SCC of treated cows tended to be lower than SCC of control cows.