It has been recognized that alpha-fetoprotein (AFP), as an oncofetal antigen, is re-expressed in large amounts in adult tumor cells and serves clinically useful purposes in tumor-marker assays. However, its biological activities are still undefined. In the present study, the ability of AFP to stimulate tumor-cell growth was observed by an in vitro experimental system. Mouse ascites cancer cells derived from hepatoma-22(H-22) or Ehrlich ascites carcinoma(EAC) were extracted intraperitoneally and cultured in RPMI 1640 medium containing 10% newborn calf serum for 48 hr. Cell growth was quantitated by a colorimetric assay using a MTT microculture tetrazolium dye. The results demonstrated that AFP significantly increased H-22-cell proliferation, with stimulation per cents of 122 to 156%. A similar growth-promoting effect of AFP was observed using EAC cells, with stimulation per cents of 86 to 210%. Moreover, the growth-stimulatory activity of AFP could be abrogated with anti-AFP antibodies. In addition, 5-fluorouracil could obviously inhibit AFP-induced proliferation of H-22 or EAC cells in vitro. These results suggest that AFP is associated with tumor-cell growth and may serve as an important target of tumor therapy.