The effect of somatostatin analog RC-160 on the growth of CFPAC-I human pancreatic cancer cells in vitro was investigated. RC-160 effectively inhibited the proliferation of CFPAC-I cells in culture, inducing a time- and dose-dependent decrease in the number of treated cells. A significant suppression of cell growth was observed after 48 and 72 hr of the exposure to (I μM) RC-160, the cell number being decreased by 38% and 46%, respectively. RC-160 was more potent than SS-14 or SMS201–995 in inhibiting the growth of CFPAC-I cells, and after 48-hr treatment the cell number decreased by 49% for RC-160 compared with 12% for SS-14 and 27% for SMS201-995. Binding experiments demonstrated that specific receptors for somatostatin were present on CFPAC-I cells. SS-14 showed a high binding affinity for [125I]-Tyr11-SS-14 receptors on CFPAC-I cells. Scatchard analysis indicated the presence of 2 classes of somatostatin binding sites on the cells, one with high binding affinity and low capacity and the other with low binding affinity and high capacity. RC-160 could bind to somatostatin receptors on these cells with an affinity similar to SS-14 but significantly higher than that of SMS201–995. Radioimmunoassay of intracellular cAMP showed that RC-160 could powerfully inhibit forskolin-stimulated cAMP production in CFPAC-I cells. Addition of forskolin to the cultures increased cAMP concentrations in the cellular lysate of treated cells. RC-160 attenuated or nullified in a dose-dependent manner the cAMP production stimulated by forskolin. Our observations indicate that somatostatin analog RC-160 inhibits the proliferation of CFPAC-I human pancreatic cancer cells in vitro and that this effect may involve the intracellular cAMP pathway.