We have previously identified the genes expressed early in the differentiation of mouse 3T3-L1 cells into adipocytes. Since these genes were isolated as small fragments, many were unknown. In this study, we have cloned two full-length cDNAs and identified them as p68 RNA helicase and mc3s5/mtCLIC. The expression of these genes was rapidly induced, and specific to the adipocyte differentiation. When the expression of p68 RNA helicase was inhibited using an inducible antisense system, the differentiation into adipocytes was partially blocked, and the expression levels of some marker genes decreased. These findings strongly indicate that the expression of the above two genes was closely related to the adipocyte differentiation, and p68 RNA helicase in particular is crucial to the differentiation.