DAIRY PRODUCTION IS MAXIMIZED WHEN COWS ARE HEALTHY AND FREE FROM INFECTION.INCREASING EVIDENCE IMPLICATES ENDOTOXIN (AN EXTRACELLULAR COMPONENT OF GRAM NEGATIVE BACTERIA) AS A KEY METABOLIC DISRUPTOR AND CAUSE OF SUBOPTIMAL LIVESTOCK PRODUCTIVITY. METABOLISM DISORDERS FOLLOWING CALVING AND HEAT STRESS ARE TWO CIRCUMSTANCES WHERE LPS (AN ENDOTOXIN)IS THOUGHT TO BE RESPONSIBLE FOR DECREASED DAIRY PRODUCTION. OUR CENTRAL HYPOTHESIS IS THAT: ENDOTOXIN REDUCES LACTATION PERFORMANCE BY DELETERIOUSLY ALTERING METABOLISM.TO TEST THIS WE WILL EXPLORE THE MECHANISMS BY WHICH ENDOTOXIN AFFECTS LIVER METABOLISM, WHOLE-BODY CARBOHYDRATE AND LIPID METABOLISM AND MAMMARY PHYSIOLOGY. THIS WILL BE ACCOMPLISHED BY INTEGRATING EXPERIMENTS USING WHOLE ANIMAL PHYSIOLOGY, MOLECULAR BIOLOGY, IN VITRO AND EX VIVO SYSTEMS. WE EXPECT TO IDENTIFY WHY INFECTION DECREASES MILK YIELD. THIS IS A SIGNIFICANT KNOWLEDGE GAP WITHIN DAIRY SCIENCE DISCIPLINE. THE POTENTIAL IMPACT OF THESE DISCOVERIES WILL LAY THE FOUNDATION FOR DEVELOPING MITIGATIONS STRATEGIES TO INCREASE EFFECIENT MILK PRODUCTION DURING SUBOPTIMAL CONDITIONS.