Genetics of NIDDM. This brief review discusses the current level of understanding of the role of genetic defects in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) and the use of molecular-genetic methods for this study. Evidence for genetic susceptibility is strong, and defects in both insulin production and action are suspect. With restriction-fragment-length polymorphisms and genomic sequencing, various candidate loci are being evaluated. Evidence that multiple genes are involved is only circumstantial. If NIDDM is genetically heterogeneous and also influenced by environmental components, population associations and linkage analyses in families may not be as easily interpreted as for diseases involving single major gene defects. 