DNA synthesis of SC-3 cells cloned from mouse mammary carcinoma (Shionogi carcinoma 115) was remarkably enhanced by androgen as well as basic fibroblast growth factor (bFGF) at the early phase (days 1-3) of stimulation in serum-free culture condition. However, bFGF-induced DNA synthesis could not be observed at the late phase (days 4-6) of stimulation while androgen was able to continuously elicit DNA synthesis. When the effect of androgen on cell yield was examined, the cell number was increased while bFGF could not enhance cell growth. Androgen-induced heparin-binding growth factor partially purified from conditioned medium behaved like bFGF in terms of DNA synthesis and replication in SC-3 cells. SC-3 cells were found to contain the high-affinity binding site toward triiodothyronine. The dissociation constant and the maximum number of the binding sites were 7 x 10(-10) M and 1800/cell, respectively. Triiodothyronine significantly blunted the testosterone-induced DNA synthesis. On the other hand, bFGF-enhanced DNA synthesis was not substantially inhibited by triiodothyronine. These results suggest that androgen, but not bFGF, has unique action site(s) which might be important for SC-3 cell replication and might be antagonized by thyroid hormone.