• A new pedigree series of bipolar manic-depressive patients admitted to the National Institute of Mental Health intramural research program was evaluated for linkage between bipolar illness and red-green color blindness, since previous studies had indicated that close linkage was generally present. Using family study methods, six informative pedigrees were investigated. Analysis was performed using a multigenerational procedure and taking into account variable penetrance. Close linkage could be definitively ruled out as a general finding. Bipolar and related illnesses are thus not generally transmitted by a single major gene close to the protan/deutan region of the human X-chromosome.