We have succeeded in cloning p90 cDNA from SK-MEL-23 cDNA library using immunoscreening method. The nucleotide sequence of p90cDNA has 100% homology to human calnexin cDNA. Calnexin is a new molecular chaperone which transiently binds nascent glycoproteins synthesized on the endoplasmic reticulum (ER) ribosome, which helps maturation of these proteins and inhibits the transportation of the misfolded or mutant protein from expressing on the correct place. Many investigators has reported that calnexin does influence maturation of secretory glycoproteins: MHC class I, II, T-cell receptor, immunoglobuline, integrine, and P-glycoprotein.We assume that calnexin might be involved in melanogenesis cascade. Tyrosinase is an unique glycoprotein which is located only on the melanosome and plays the most important role in melanogenesis cascade. In order to examine the interaction between calnexin and wild-type tyrosinase, COS7 cells were transfected with calnexin cDNA alone or calnexin plus human wild-type tyrosinase cDNA. The co-transfectant revealed higher tyrosinase activity than the single on the dopa assay. On melanin assay the co-transfectant synthesized more melanin than the single transfectant. On immunoprecipitation calnexin showed the binding with tyrosinase. Castanospermine, a glycosidase inhibitor, prevented tyrosinase from maturation.With these results, we conclude that calnexin binds tyrosinase in ER. Furthermore, we propose that calnexin might be involved in inhibition of the transportation of the mutant tyrosinase to melanosome by retaining in the ER.