Bioactive compounds that may control the specific differentiation from mouse embryonic stem (ES) cells into cardiac-like cells have been screened from herbal medicines. Among seven preparations, Panax ginseng was found to promote the differentiation into beating cells and to sustain their beating for longer than the control. Active compounds were found in its water-soluble fraction. Although they were not isolated, their candidates were surveyed in 42 compounds selected from the database of P. ginseng. Finally we found that vitamin B₁₂ (VB₁₂) and methionine were active. VB₁₂ accelerated the differentiation into beating cells and made the beating rate constantly 100%. Moreover, VB₁₂ was effective in the recovery of beating that was inhibited by spermine action. The mechanism of action of VB₁₂ is discussed in termo of the relevance of intercellular electrical signal transduction.