AbstractWe have studied the effect of increased intracellular levels of cyclic AMP on the growth response to platelet‐derived growth factor (PDGF) of human foreskin fibroblasts in culture. It was found that forskolin, a potent stimulator of adenylate cyclase activity, inhibits the stimulatory effect of PDGF on3H‐thymidine incorporation with a dose dependence similar to that observed with regard to cyclic AMP formation. A time‐course study indicated that forskolin has no effect on ongoing DNA synthesis but affects events in the prereplicative phase. The cell‐cycle block induced by forskolin was found to be reversible; after removal of the drug, DMA synthesis was initiated after a lag period, similar to that of the prereplicative phase of control cells. Forskolin had no effect on PDGF binding, receptor autophosphorylation, or c‐fosmRNA expression. However, a reduction in PDGF‐induced c‐mycmRNA expression was observed in cultures given forskolin. Forskolin was also found to have a marked stimulatory effect on the expression of interferon‐β2mRNA expression. However, we were unable to demonstrate that the growth‐inhibitory effect of forskolin is mediated by interferon‐β. In conclusion, an increase in cAMP levels leads to a reversible inhibition of PDGF‐induced DNA synthesis in human fibroblasts, which may be related to an inhibition