The absorption rates of two model drugs, salicylate and antipyrine, from the small intestines of rats deprived of food for various periods of time were compared with rats fed ad libitum. Fasting reduced the absorption rate constants for both drugs with the salicylate rates being depressed more severely than the rates for antipyrine. Intestinal mass studies showed that the weight/length ratio of the rat intestine is progressively decreased as fasting is prolonged up to 96 hr. The intestinal weight loss was much more pronounced than the total body weight loss. The loss in intestinal weight and the observed decrease in drug absorption rate are believed to be related to the inhibition of intestinal cell proliferation due to fasting, resulting in a decreased absorptive surface and reduced mucosal cell viability.