Abstract: Hormogonia differentiation in Nostoc sphaeroides can be inhibited by calmodulin antagonists W-7 and Fluphenazine (FPZ). FPZ fluorescence showed that the cellular calmodulin distributions were less than that of control after treatment of calmodulin antagonists. When reached to a certain concentration, the chelator EGTA could also block the differentiation of hormogonia. As shown by CTC fluorescenc e, the membrane-bounded Ca2+of algal cells was significantly decreased after treatment of EGTA. The results suggested that the complete differentiation of hormogonia was a process coordinated by several metallic ions. Nitric oxide (NO) could decrease the rate of hormogonia differentiation to a large extent, but at the same time, NAA, an inhibitor of nitric oxide synthetase (NOS), also could completely inhibit the differentiation. The differentiation process could be inhibited by exogenously added reactive oxygen intermediates (ROIs), while catalase (CA), the scavenger of ROIs, stopped the differentiation process too. The above results implied that the differentiation process of hormogonia in Nostoc sphaeroides was mediated by a complicated signal transduction system.