A double-blinded randomized prospective clinical trial was designed to evaluate the effectiveness of flunixin meglumine and phenylbutazone for treatment of acute toxic mastitis in dairy cows. All cows were treated 4 times at 12-hour intervals by intramammary infusion of gentamicin (150 mg). A total of 45 dairy cows with toxic mastitis were randomly assigned to 1 of 3 treatment groups: group 1 (control), saline solution, IV; group 2, 1 g of flunixin meglumine, IV; or group 3, 4 g of phenylbutazone, IV. Physical examination and udder variables were assessed at initial examination and 24 hours later. Milk production was recorded at regular intervals from 1 week before until 10 weeks after development of mastitis. Rear quarters (34/45) were more commonly affected than front quarters. Thirty-five cows returned to the herd, 9 cows were culled, and 1 cow died. There were no significant differences among treatment groups in the need for further treatment or outcome. Klebsiella spp (18/45) and Escherichia coli (16/45) were the most common pathogens isolated by culture of milk from affected quarters. The overall bacteriologic cure rate on days 7 and 14 was 64 and 75%, respectively. At the time of initial examination, cows of the control group had higher rectal temperature than did cows of the flunixin group. At the examination 24 hours later, the rectal temperature of cows in all treatment groups was lower than the temperature at initial examination; at that time (24 hours), however, there were no significant differences in temperature among the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)