The treatment of human fibroblasts with different tocopherols in the presence of retinol caused an increase in cytoplasmic retinoic acid binding protein II (CRABP-II) mRNA and protein. The possibility of an involvement of protein kinase C (PKC) in the response to tocopherols was supported by the results obtained with the PKC-specific inhibitors, calphostin C and bisindolylmaleimide I. The effect of alpha-tocopherol was prevented by okadaic acid, suggesting that a protein phosphatase is responsible for PKC dephosphorylation produced by the presence of tocopherols. The results shown support the hypothesis that phosphorylation/dephosphorylation of RXRalpha via PKC may be involved in the regulation of CRABP-II gene expression.