Immunohistochemical and biochemical approaches were utilized to compare the expression of microsomal triglyceride transfer protein (MTP) and cellular retinol binding protein II (CRBPII) with the expression of apolipoprotein (apo)B and apoA-I along the entire length of the small intestine in mice. MTP is expressed in villus-associated enterocytes along the length of the small intestine. Maximal expression occurs within the first 20% of the intestine and decreases to less than 3% of maximum in the distal third of the intestine. The expression of CRBPII is nearly identical with that of MTP. Peak expression of apoB and apoA-I occurs in the first 25% of the intestine; however, expression in the most distal segments of the intestine is 10%-15% of maximum expression. In mice fed a Western diet for 3 weeks the expression of MTP and CRBPII was elevated in the distal regions of the intestine, whereas the expression patterns for apoB and apoA-I were similar to those found in mice on control diets. We conclude that the patterns of expression, as well as the regulation of MTP and CRBPII, are similar. However, the expression and regulation of these two proteins differ from those of apoB and apoA-I. In particular, the expression of MTP is not coordinated with the expression of apoB, even though the two proteins are essential for the assembly and secretion of chylomicrons.