Chronic oral intake of morphine sulphate leads to tolerance toward intestinal action and reduced nutritional uptake. The mechanism involved in this tolerance was clarified by studying the levels of intestinal cellular macromolecules and activities of intestinal membrane-bound key enzymes connected with the transport of nutrients. In vivo intestinal absorption of [¹⁴C]glucose and [¹⁴C]glycine was examined to study the precise relationship between involvement of enzymes and transport of these labelled nutrients. Male Wistar rats were made morphine dependent. The levels of carbohydrates and glycogen and activities of adenosine triphosphatase, Na⁺K⁺-dependent ATPase, and alkaline phosphatase were decreased in the morphine-treated rats. This altered enzyme activity concurred well with the absorption of labelled nutrients and was reflected in the cellular macromolecular levels of carbohydrates and glycogen. Results from this study indicate that animals develop tolerance through DNA, RNA, and protein synthesis and altered nutritional uptake through defective enzyme machinery, thus explaining the adverse effect of morphine sulphate.