During our search for a marker for non-insulin-dependent diabetes mellitus (NIDDM) in a large multigenerational family with a form of NIDDM termed maturity-onset diabetes of the young (MODY), we learned a great deal that may serve to streamline the search for diabetes-susceptibility genes in other families. We describe here our experience and suggest strategies that may enhance the search for markers for other diabetes susceptibility genes with genetic linkage approaches.