In order to define the islet amyloid polypeptide (IAPP) levels in gestational diabetes mellitus (GDM) and their interrelationship with the insulin levels, we studied (1) the placental RNA from 10 women (5 with GDM and 5 normals) for IAPP expression by Northern blotting and (2) 10 women with GDM during a 100-gram oral glucose tolerance test and compared these with 11 normal women matched for obesity and age. Plasma levels of glucose, IAPP, insulin, and C peptide were determined. No IAPP expression was detected in any of the placentae after a long exposure. We could not demonstrate any differences in plasma IAPP levels (basal or stimulated) between the two groups of pregnant women. However, in women with GDM we found a lower IAPP/insulin ratio (p < 0.05) and a lower maximal IAPP/maximal insulin response ratio during the oral glucose tolerance test (p < 0.05) than in normal women. Therefore, IAPP does not appear to be directly involved in the development of GDM. The peripheral levels of IAPP relative to insulin are lower in GDM, a finding similar to that described in type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus). This observation further confirms that GDM resembles the early stages of type 2 diabetes mellitus.