Incubation of BHK-21 hamster fibroblasts in a serum- and amino acid-deficient medium caused a 3-fold increase in the degradation of endogenous protein, a doubling of the degradation of endocytosed epidermal growth factor, and an eightfold increase in the degradation of endocytosed alpha 2-macroglobulin. 3-Methyladenine (3MA) inhibited the deprivation-induced lysosomal degradation of both endogenous and endocytosed protein, but had no effect on basal (non-induced) degradation. 3MA also inhibited deprivation-induced protein degradation in human IMR-90 fibroblasts. Some inhibition of protein synthesis and of endocytic uptake of alpha 2-macroglobulin was observed in 3MA-treated BHK-21 cells, whereas cellular ATP levels were unaffected. These results are different from those obtained with isolated hepatocytes, and suggest that in some cells both endogenous and endocytic protein degradation may be accelerated as part of a general deprivation response.