In this study we examined the ability of intraperitoneal cholecystokinin COOH-terminal octapeptide (CCK-8; 0.2, 0.6, and 2.0 micrograms/kg) to suppress food intake in rats that had consumed a control diet, 6-8 g.kg-1.day-1 of ethanol (EtOH) in sucrose, or sucrose alone for 6 mo. Both the EtOH- and sucrose-fed rats developed significant dietary obesity. After 3 mo, the EtOH group was significantly more sensitive to CCK-8 than the sucrose and control groups, while the responses of the sucrose and control groups were comparable. In contrast, after 6 mo the EtOH and sucrose groups' response to CCK-8 was no longer significantly different. After 6 mo there were no significant differences in basal or postprandial plasma CCK-8 levels. The sucrose group had significantly higher basal insulin levels than the control and EtOH groups, and postprandial insulin levels, relative to basal, were significantly elevated in the EtOH group. Basal glucose levels did not differ among groups. Postprandial glucose levels (relative to baseline) were significantly lower in the EtOH group compared with the other groups and in fact never rose above baseline levels. These results are consistent with the hypothesis that EtOH, when taken on a chronic basis, increases the sensitivity to CCK-8.