The overall rates of protein synthesis and degradation in perfusion-grown WI-38 cells were followed in the three days after a stepdown in the serum concentration of the culture medium, from 10% to 0.3%. Within three hours after the stepdown, the rate of protein synthesis had decreased and the rate of protein degradation had increased, the combined result being the cessation of protein accumulation. The degradation rate returned over the next three days to its original value, but a zero rate of accumulation was retained because the synthesis rate continued to decline. The rate of DNA synthesis remained constant for six hours after the stepdown. It then declined steadily until reaching a minimum about eight hours later. The results show that extracellular control of protein accumulation depends on adjustments in both protein synthesis and protein degradation, and that the adjustments take place rapidly. This behavior suggests that the cell cycle is arrested after a stepdown because post-mitotic cells are unable to accumulate additional protein. However, an alternative interpretation of the data is that at least part of the changed accumulation is the result, rather than the cause, of the cycle arrest, and that the arrest is caused by other, more specific, reactions than those of general protein metabolism.