We describe a "physiological" cell cycle synchronization model system. FRTL5 cells, TSH-dependent for proliferation, were starved from TSH. The cell cycle phases and the expression of markers associated to different cycle phases were evaluated. TSH starvation blocks proliferation without provoking death and induces virtually all the cells to accumulate in G0/G1 phase. TSH readdition allows 30% of these cells to enter the S phase. DNA topoisomerase II 170-kDa isoform is not expressed in G0/G1 synchronized cells while it is expressed in logarithmic growing cells. The 180-kDa isoform is not expressed in G0/G1 synchronized cells while it is expressed in 20% of logarithmic growing cells regardless of the cycle phase. c-myc mRNA is not expressed in G0/G1 synchronized cells while it is detectable upon TSH readdition. This system provides a tool for the analysis of events associated with the G0/G1 phase and the transition from G0/G1 to S phase.