Steele, M. A., Greenwood, S. L., Croom, J. and McBride, B. W. 2012. An increase in dietary non-structural carbohydrates alters the structure and metabolism of the rumen epithelium in lambs. Can. J. Anim. Sci. 92: 123-130. This study investigated the effect of a grain challenge on the structure and metabolism of the rumen epithelium in lambs. In a randomized design, lambs (n = 8) received either a control diet [30% dry matter (DM) grain], or a diet of increasing amounts of grain to a maximum inclusion of 79% of DM for 12 d prior to slaughter. Rumen papillae were collected from the ventral sac on day 13 and prepared for histological and gene expression analyses. All lambs fed the high-grain diet were diagnosed with ruminal parakeratosis as the thickness of the corneum was higher (P<0.01) compared with control lambs (51.0±2.3 vs. 17.3±2.5 µm). Plasma beta-hydroxybutyric acid concentrations increased linearly (P<0.05) with increased grain consumption compared with the control. However, the relative mRNA expression of the ketogenic enzyme 3-hydroxy-3-methyl-glutaryl CoA-synthase (HMGCS2) in rumen papillae was not different between treatments. The expression of cholesterolgenic enzyme HMGCS1 was down-regulated by 0.70±0.06 (P<0.05) fold in lambs fed the high-grain diet compared with the control. These results suggest that a short-term grain challenge in lambs is associated with altered rumen epithelium metabolism and structural changes indicative of ruminal parakeratosis.