Insulin-like growth factor-I (IGF-I), which mediates the synthesis of DNA and enters the S phase from the G₀/G₁ phase of the cell cycle, is a potent growth factor that promotes cell cycle progression in various types of mammalian cells in culture. On the other hand, when IGF-I is removed in the middle of the G1 phase, cells stop progressing the cell cycle. We have previously demonstrated that basic fibroblast growth factor (bFGF) accelerated the cell proliferation, cell cycle progression, and expression of cell cycle regulating proteins and genes in gingival fibroblasts derived from nifedipine reactive patients (nifedipine responder; NIFr) compared with those in nifedipine non-reactive patients (nifedipine non-responder; NIFn) . In the present investigation, we studied differences of cell growth, cell cycle, and expressions of cell cycle regulatory proteins and genes stimulated by IGF-I in NIFn and NIFr cells to demonstrate that cell growth, DNA synthesis, and progression to S and G₂/M from G₁ of the cell cycle were significantly enhanced in NIFr cells compared with those in NIFn cells in the presence of IGF-I. The phospho-ser780-Rb protein level of NIFr cells increased compared with that of NIFn cells by IGF-I stimulation. The expression levels of other cell cycle control factors, proteins (E2F-1, Rb) and genes (cdks 1, 2, 4, 6 and cyclins A, B1, D1, E), similarly increased in both NIFn and NIFr cells by IGF-I. Thus, the mechanism of gingival overgrowth caused by nifedipine may be related to ser780-phosphorylated Rb of NIFr cells.