This study examines the effect of prolonged absence of oral food intake on structural parameters of the gastrointestinal tract in rats maintained nutritionally by intravenous feeding for up to 3 weeks. During this time, their body weights increased by 22%. Controls fed a nearly isocaloric oral diet were sham operated and harnessed in the same manner as their parenterally fed counterparts. Parenteral feeding resulted in a significant decrease in the weights (per 100 g body weight) of the oxyntic gland area of the stomach, small intestine, and pancreas. The weights of the spleen, testes, kidneys, and antral region of the stomach were unaltered. In the small intestine there was a significant loss of DNA and a near doubling of the RNA:DNA ratio in the parenterally fed animals. In the absence of an oral diet antral gastrin levels decreased to one-thirtieth of the control level. The following conclusions are suggested by these results. First, the oral intake and/or physical presence of food within the gastrointestinal tract are necessary for structural maintenance of some tissues of that tract. Second, the disproportionate decrease in weight that occurs in certain tissues is apparently unrelated to the absence of nutrients which might normally be utilized directly from the lumen. Third, maintenance of normal tissue stores of the hormone, gastrin, is dependent on stimuli provided by oral ingestion and the presence of food in the gastrointestinal tract.