The cholera toxin (CT) is a well-known inducer of cAMP and cAMP regulates gene expression of many genes. However, little is known as to the alterations in gene expression in response to CT. Here the alterations of the expression of 800 selected genes in response to CT were examined using cDNA microarrays. Gene expression alterations in human lymphocytes and monocytes were found after exposure to CT at varying concentrations for different time periods. Over 200 genes showed varying degrees of alterations of expression in CT-treated cells. The CT-induced changes in gene expression were compared by cDNA microarrays under the same conditions to those in response to forskolin, a specific activator of adenylate cyclase, and MDL-12, an irreversible inhibitor of adenylate cyclase. Thirty-five CT-responsive genes were found responded similarly to forskolin but differently to MDL-12. Fourteen CT-responsive genes were affected similarly by MDL-12 but differently by forskolin. Many of these CT responsive genes were involved in immunity, inflammation and oxidative stress. The CT induced responses correlated with those induced by CT subunits. The down regulation of Th1 markers and upregulation of Th2 markers by CT are consistent with the CT induction of Th2 cells.