Three studies are described in this report. First, the effect of intravenous administration of the steroidal drug isoflupredone acetate on healthy lactating dairy cows and lactating dairy cows with mastitis induced using bacterial endotoxin was investigated. When compared with untreated mastitic controls, cows with endotoxin-induced mastitis treated with 20 mg isoflupredone acetate after the development of clinical signs did not exhibit measurable differences in heart rate, rectal temperature, rumen motility, or changes in mammary gland surface area in the 14 hours following the administration of intramammary endotoxin, nor did they have significantly different milk production following the mastitic episode.;In the second study, somatic cell counts and flow cytometric analysis of cytokeratin-positive epithelial cells in the milk of lactating Holstein cows were performed before and 12 hours after the induction of mastitis using purified bacterial endotoxin. Twelve hours after the induction of mastitis, the mean percentage of cytokeratin-positive cells had increased from 4.18% +/- 1.05 to 40.63% +/- 10.23, and the mean number of cytokeratin-positive cells per milliliter of milk had increased from 7,711 +/- 2,575 to 2,954,554 +/- 877,719. Treatment with flunixin meglumine or isoflupredone acetate after the development of clinical signs of mastitis did not mitigate the significant increases in somatic cell count or cytokeratin-positive cells in milk in the first 12 hours following endotoxin administration.;Finally, the effects of flunixin meglumine and isoflupredone acetate were compared in lactating Holstein dairy cows with mastitis induced by the intramammary administration of purified bacterial endotoxin. Drugs were administered to cows following the development of mammary swelling and a rectal temperature of 40°C or greater. Neither drug decreased milk production loss nor mammary surface swelling when compared to untreated mastitic controls. Both drugs reduced the mean heart rate in treated groups over the 14 hours following endotoxin administration, when compared to untreated mastitic controls. Animals treated with flunixin meglumine also had increased rumen motility and decreased rectal temperature over the same time period, when compared to untreated mastitic controls or mastitic cows treated with isoflupredone acetate.