A study of the effects of ADP and cyclic AMP related drugs on gel formation induced by endotoxin and amebocytes aggregation was conducted. The gel formation induced by endotoxin could be inhibited by ADP, cyclic AMP, ATP and aminophylline. Conversely, Phosphodiesterase enhanced gelation rate. A calmodulin antagonist, trifluoperazine, also inhibited endotoxin-induced gel formation, but this agent was able to induce potentiation in amebocytes aggregation. These results suggest that the cyclic AMP phosphodiesterase system may play an important role in endotoxin-induced gel formation, and it was concluded that, in the presence of both Ca++ and endotoxin, the calmodulin-like protein will activate the cyclic AMP phosphodiesterase system and decrease the concentration of cyclic AMP, thus promoting gel formation.