In the nonanesthetized rat, the jejunal permeability to four simultaneously administered molecules, mannitol, phenol red, inulin and PVP, was measured by analyzing blood, serum, urine and duodenal fluid for these compounds. Of the molecules which had entered the body, approximately 50% were found in the urine, another 50% in the extracellular space and only about 1% were excreted into the duodenal juice. The intracellular content of the molecules is not accounted for in these numbers. The rate of permeation decreased with increasing molecular weight of the substances. EDTA (25 mmol/l) and deoxycholate (5 mmol/l) increased the jejunal permeability for these molecules but not for mannitol. The alterations in mucosal cell turnover and morphology induced by hydroxyurea did not change jejunal permeability for mannitol and phenol red at any time. 24 and 48 h following hydroxyurea, jejunal permeability for inulin and PVP was decreased.