Pharmacological doses of dexamethasone (dex) are commonly used to treat very low birth weight infants during the first weeks of life. Although its beneficial pulmonary effects are well recognized, detrimental effects are seen in other tissues. Our goal was to develop a piglet model in which to study the protein catabolic effects of dex. Experiment 1: Nine female piglets(1500-2165g) were removed from the sow within 12h of birth and fitted with umbilical catheters for blood sampling and dex administration. Pigs were housed in individual cages which allowed for control of intake and quantitative urine collection. A 5 day baseline preceded the 7 day treatment period. Five pigs received dex (1mg/(kg*d)) and 4 pigs served as saline controls. Daily fasting (7h post feeding) and fed (1h post) blood samples were obtained. Dex administration resulted in 40% reductions in weight gain (72 vs. 43 g/(kg*d), p=0.0004) and snout to rump length (1.15 vs. 0.61 cm/d, p=0.015). Fasting BUN (mg/dl) was elevated within 24h after dex (2.2 vs. 4.1, p=0.002), and continued to rise (d6: 2.2 vs. 11.7, p=0.0001). Cumulative urinary N excretion (g/kg) in the dex treated pigs was 3 times greater than in controls(1.7 vs. 5.5, p=0.0001). Fasting blood glucose was not altered by dex; however, the average fed state blood glucose was ≈20% higher. In the fed state, plasma insulin was elevated and a doubling of the insulin:glucose ratio was observed (12 vs. 26 pmol:mmol, p=0.02). Experiment 2: After catheters were secured, piglets returned to the sow for the entire study. The design was modified to include 4 day baseline, treatment, and recovery periods. Female piglets (n=21) were studied. One of 4 levels of dex (0, 0.25, 0.5, 1 mg/(kg*d)) was given. A 25-75% rise in BUN from baseline was evident by 12h in all dex groups (p=0.0001). BUN rose over time in the dex pigs with no differences between the 0.25 and 0.5 groups. With removal of dex, BUN returned to baseline in 3 to 4d. The ratio of insulin:glucose doubled by 12h of dex treatment, was maintained, and returned to baseline 24h into recovery. Linear growth was affected by dose during treatment (1.2, 0.66, 0.44, 0.29 cm/d); all pigs grew at the control rate during the 4d recovery. Dex treatment altered metabolism as seen by elevations in BUN and N excretion, and disruption of glucose and insulin homeostasis. Marked reductions in weight gain and linear growth were observed. It is anticipated that dex treatment will result in increased amino acid oxidation and decreased muscle protein synthesis in the piglet model.