A polarized differentiated subclone of HT29, a human colon carcinoma cell line, was used to measure the passage of drugs across the intestinal epithelium. These cells, HT29-18-C1, when grown on permeable filters, formed tight monolayers of high electrical resistance (> 400 omega cm2). Electron micrographs revealed the presence of numerous apical microvilli and well developed junctional complexes. The transepithelial passage of various drugs was studied: the transepithelial permeability coefficients ranged from 0.8 x 10(-6) cm/s for fluorescein, to 4.8 x 10(-5) cm/s for the most lipophilic molecule, testosterone. For the five compounds tested, there was a coarse correlation between the apparent transepithelial permeability coefficient and the octanol/buffer distribution coefficient. The HT29-18-C1 subclone thus represents a new in-vitro model for studying the intestinal absorption of drugs.