Manic depressive illness is a common and frequently debilitating familial psychiatric disorder. Efforts to understand the mechanisms of inheritance have been hindered by the complexity of the phenotype, which may range from benign mood swings to chronic psychosis, and by apparently nonmendelian modes of transmission. Early reports of linkage to chromosomal loci have fallen into doubt; however they have helped encourage the development of more sophisticated methods for analyzing complex phenotypes. Using such methods, linkage of manic depressive illness to loci on chromosome 18 has been reported and apparently replicated, and work is proceeding to identify genes associated with what is probably a genetically heterogeneous set of disorders. As molecular mechanisms of inheritance are elucidated, it will be important to consider the ethical implications of genetic testing in a clinically and genetically complex disorder such as manic depressive illness.