Gap junctional intercellular communication(GJIC) provides a mechanism for regulating multicellular activities by allowing the exchange of small diffusible signaling molecules between neighboring cells. This study was conducted to assess the GJIC during the differentiaion of F9 cells. F9 cells derived from mouse embryonic teratocarcinoma were stimulate to differentiate to visceral or parietal endoderm by retinoic acid and by retinoic acid and dibutyryl cyclic AMP, respectively. The differentiation states of F9 cells were monitored by the cell morphology and by the expression level of collagen type Ⅳ(α_2). When GJIC was assessed by measuring the transfer of scrape-loaded lucifer yellow dye, differentiated cells showed decreased communication as compared with undifferentiated cells. Northern blot analysis revealed the decrease of the connexin 43 transcript during the both differentiation processes. Western blot analysis also showed that the cellular amount of connexin 43 protein was decreased as F9 cells differentiated to parietal endoderm or visceral endoderm. Data suggest a constitutive disruption of connexin 43 during chemical induced differentiation in F9 cells.