Dietary sphingomyelin (SM) undergoes sequential cleavage to ceramide and sphingosine in the intestine. A distinctive intestinal sphingomyelinase (SMase) with alkaline pH-optimum was earlier identified by us. The activity was higher in middle and lower small intestine, but its role in SM digestion has not been clarified. In this study we examined the extension and capacity of SM digestion has not been clarified. In this study we examined the extension and capacity of SM digestion in vivo. After feeding rats 0.2, 6.6, or 32 mu mol SM containing 2 mu Ci(3)H-sphingosine-labeled milk SM (H-3-SM), radioactivity was analyzed in intestinal contents and tissues 2, 4, and 8 hr later. The proportion of radioactivity in the contents of small intestine increased with the dose of SM; 9% of given dose with 0.2 mu mol, 34% with 6.6 mu mol, and 71% with 32 mu mol, respectively after 2 hr. Lowest tissue radioactivity was found in duodenum and proximal jejunum and highest in distal jejunum and proximal ileum. Three to twenty one percent of radioactivity in the intestinal tissue was in ceramide, the proportion varying with the dose given, region of the intestine, and time after administration. After administration of 6.6 or 32 mu mol SM, significant amounts of intact SM and ceramide was found in intestinal contents, colon, and excreted faeces. Colon was exposed to ceramide derived from exogenous SM in amounts that were rather proportional to the dose of SM fed. SM digestion is thus a process extending over the whole intestine and occurring mainly in the middle and lower parts of the small intestine. The site of digestion coincides with the distribution of the alkaline SMase, indicating that this enzyme catalyzes the first step in the digestion. The extension and limited capacity of the SM digestion leads to an exposure of the lower small intestine and colon to SM and sphingolipid metabolites. (C) Elsevier Science Inc. 1997.