Our objective was to study whether islet amyloid polypeptide (IAPP) produces satiety by an endocrine mechanism. We used a rat model to determine whether postprandial plasma levels of IAPP are comparable to those required to inhibit feeding when IAPP is administered by continuous intravenous infusion. Food intake in rats with aortic catheters increased plasma IAPP levels from a fasting level of 10.8 +/- 0.5 pM to a peak level of 19.0 +/- 1.0 pM at 2.2 +/- 0.5 h. in rats with jugular vein and aortic catheters, the threshold intravenous dose for IAPP suppression of feeding was between 1 and 3 pmol . kg(-1). min(-1). The 3 pmol . kg(-1). min(-1) dose decreased 4-h intake by similar to 25% by decreasing meal frequency rather than meal size. This dose increased plasma IAPP by similar to 24 pM. These results suggest that postprandial plasma levels of IAPP are not quite sufficient to independently produce satiety.