Insulin promotor factor-1 (IPF-1) is a gene critical for pancreatic development and insulin transcription. We genotyped U.S. Caucasians with (n = 217) and without (n = 176) Type 2 diabetes to determine if three previously identified variants (Cys18Arg, Asp76Asn, Arg197His) in the IPF-1 gene play a role in the development of Type 2 diabetes. The Cys18Arg and Arg197His variants were not present in any subjects. The Asp76Asn variant was found in one control subject (0.9%) and none of the diabetic subjects. Similarly, none of the variants were detected in African American subjects with (n = 78) and without (n = 82) Type 2 diabetes. In conclusion, these variants are rare or absent in U.S. Caucasians and African Americans and therefore, unlikely to play a significant role in the development of Type 2 diabetes in these populations.