The combined effects of the growth factors, PDGF, TGF-beta and IGF, on the metabolism of two androgen substrates by human gingival tissue were investigated. Having established their wet weight, duplicate incubations were performed in Eagle's MEM using [(14)C]testosterone/[(14)C]4-androstenedione as substrates and growth factors, PDGF, TGF-beta and IGF, alone and in combination. Steroid metabolites were then isolated, separated and quantified, using a radioisotope scanner. With [(14)C]testosterone as substrate, there were 3-5-fold decreases in 5alpha-reductase activity in response to individual growth factors, while the combinations, PDGF+TGF-beta, PDGF+IGF and TGF-beta-IGF, resulted in approximately half the stimulation, or similar to that of one of the growth factors, but still about 2-fold greater than control values. When [(14)C]4-androstenedione was used as substrate, there were approximately 2-6-fold increases in DHT synthesis in response to the growth factors alone. When used in combination, and intermediate response was seen. Growth factor combinations can enhance anabolic activity in the chronically inflamed periodontium.