BACKGROUND: Familial correlations, twin studies and adoption studies have all indicated that human obesity has a substantial genetic component. To date, obesity genes have only been identified using mouse models. METHODS: In an attempt to identify human obesity genes large numbers of multigenerational families, in whom extreme obesity segregates, are currently being collected. RESULTS AND CONCLUSIONS: Relative risk estimates and models of genetic heterogeneity indicate that at least 500 affected sibling pairs will need to be collected to identify major genes.