We have utilized antibody probes to examine the expression of DNA topoisomerases I and II and chromosome scaffold protein Sc-2 in normal and transformed cells. Neither topoisomerase I nor Sc-2 shows significant fluctuations in content or stability across the cell cycle. In contrast, topoisomerase II undergoes significant cell cycle-dependent alterations in both amount and stability. As cells progress from mitosis into G1, much of the topoisomerase II is degraded. During the first 2 hr of G1, the half life of topoisomerase II is decreased from that measured in asynchronous cell populations by a factor of 7. This suggests that the chromosome condensation/decondensation cycle is coupled to a parallel cycle of synthesis and degradation of topoisomerase II. In control experiments, we also found that the half-life of topoisomerase II is shorter in normal cells than in transformed cells by a factor of 4. Since the number of copies of topoisomerase II per cell is also lower in normal cells, this suggests that control of topoisomerase II stability is altered upon transformation. The stability of topoisomerase I and Sc-2 does not differ significantly between normal and transformed cells.