The nutritional role of intestinal lysosomal enzymes in the regulation of reversible adaptation to starvation and realimentation by various dietary treatments is investigated. When rats were starved for periods ranging from 72 to 120 h, the specific activity of the representative lysosomal hydrolases, viz. acid phosphatase, β-glucuronidase, β-galactosidase, arylsulfatase, and cathepsin D of small intestinal mucosa, progressively increased reaching levels two to four times higher than the fed controls. During the starvation period of only 72 h, more than 60% of the intestinal weight and about 75% of the mucosal protein was lost. On realimentation with a complete diet such as laboratory rat chow, the specific activity of the intestinal lysosomal enzymes rapidly returned to normal and the lost weight of the intestinal tissue and of the body as a whole was restored. The regulatory effect of major dietary nutrients such as carbohydrates, proteins, and fats on the starvation-induced breakdown of the intestinal tissue reserves is presented and discussed. The findings of this study indicate that changes in the specific activity of the intestinal lysosomal enzymes are associated with adaptive processes requiring rapid turnover of body tissues for maintenance and survival of the animal during starvation and/or during conditions when dietary supply of certain nutrients is limited.