The kinetics of cell cycle progression in continuously proliferating 3T3 fibroblasts and two tumor transformed derivatives (3T6 and SV 3T3 cells) following treatment by growth-factor deprivation (serum starvation) or 25-hydroxycholesterol were studied. Normal 3T3 cells were found to respond immediately (in the first cycle) to growth factor deprivation by leaving the cell cycle from G1, whereas the tumor transformed derivatives did not. However, all three cell types were forced to stop the progression through the beginning of G1 when treated by 25-hydroxycholesterol. It was ensured that the doses of 25-hydroxycholesterol used really induced substantial decrease of HMG CoA reductase activity. However, the effects of serum starvation on HMG CoA reductase activity varied considerably. In 3T3 cells HMG CoA reductase activity was substantially depressed, in 3T6 cells it was moderately depressed, and in SV-3T3 cells it was not depressed at all. This difference of HMG CoA reductase activity between 3T6 and SV-3T3 cells was related to the difference of growth activity in serum-free medium. The data indicate that a certain activity of HMG CoA reductase is required for the proliferation of normal as well as tumor transformed cells but also that impairment of the control of HMG CoA reductase, leading to increased enzyme activity, may result in uncontrolled growth in tumor transformed cells.