Pedigrees of manic-depressive patients in treatment at the Lithium Clinic of the Institute of Clinical Pharmacology, University of Cagliari, were evaluated for linkage between major affective illness and the protan-deutan-glucose-6-phosphate-dehydrogenase region of the X-chromosome. Two informative pedigrees were found, investigated and analyzed for linkage using a multigenerational model and considering age-dependent penetrance. The results are consistent with the hypothesis of X-linkage in major affective illness.