Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) interact to stimulate proliferation of fibroblasts in culture. Glucocorticoids variably effect the response of cultured fibroblasts to polypeptide growth factors. This study determined the effects of dexamethasone on growth-factor stimulation of gingival, periodontal ligament and pulp fibroblast proliferation in vitro. Cultures of quiescent, low-passage, human fibroblasts were treated for varying periods of time with transforming growth factor-beta 2 (TGF-beta 2), PDGF and IGF-I: (1) alone, (2) in combination with each other, (3) singly plus dexamethasone, (4) in combination plus dexamethasone. Combinations of human, recombinant PDGF and IGF-I (10-1000 ng/ml) induced significantly higher rates of cell proliferation than either factor alone. Dexamethasone at doses ranging from 10(-5) to 10(-8) M substantially enhanced cell proliferation induced by these combinations and by PDGF without IGF-I but not IGF-I alone. By 6 days after a single application, 2-3 times as many cells were present in the PDGF and dexamethasone cultures as compared to PDGF without IGF-I. TGF-beta 2 specifically blocked the effects of dexamethasone added to PDGF-stimulated cells. Collagen and non-collagenous protein synthesis was not affected by the addition of PDGF and IGF-I with or without dexamethasone. These data suggest that dexamethasone may substitute for IGF-I in PDGF stimulation of cell proliferation.