The role of the lysosomal system in accelerated protein degradation was investigated in 3T3 mouse fibroblasts and in the SV40 virus-transformed derivative, SV3T3. Rates of protein degradation and quantitative electron microscopic alterations in the lysosomal system were compared under four different growing conditions: exponential growth, confluent phase, serum deprivation, and confluent phase together with serum deprivation. We found a significant correlation between increases in rates of proteolysis of long-lived proteins and fractional volume of lysosomes, suggesting a causal relationship between the two, as well as a morphological explanation for the differences in rates of protein degradation in transformed and non-transformed cultured cells. The increase in lysosomal fractional volume resulted from an increase in dense bodies only (in serum-deprived exponential or confluent cultures) or from an increase in autophagic vacuoles and dense bodies (in serum-supplemented confluent cultures).