An amino acid sequence (Arg-Gly-Asp-Val) specifically associating with cell adhesion between cells and extracellular matrices was found on the human Zn-alpha 2-glycoprotein (Zn alpha 2gp) molecule. Although other mammalian cell lines such as breast carcinoma and melanoma did not, SMKT R-3 cells (human renal cell carcinoma) but not the kidney cell lines (Vero and COS7) preferentially attached and spread on a tissue culture plate coated with either blood plasma Zn alpha 2gp or seminal plasma Zn alpha 2gp. The spreading of SMKT R-3 cells on Zn alpha 2gp required divalent cations such as Mn2+ and Mg2+, and this spreading was inhibited by synthetic peptides such as RGDS, LRGDV and ELRGDV. These findings suggested that the RGDV region mainly interacted with the cell surface integrins to regulate cell attachment and spreading.