Studies with X-chromosome markers in mental illness have been limited to the diagnostic concept of primary affective disorders. The present study is the first to our knowledge to demonstrate statistically measurable linkage between color blindness and manic-depressive illness in a family identified by a schizo-affective proband. Linkage data and lithium carbonate response in the proband suggest that the schizophreniform-affective spectrum in members of the pedigree may reflect a genetically distinct disorder. The use of a genetic marker as a heuristic diagnostic criterion in a subgroup of heredofamilial psychoses with unclear diagnostic boundaries is proposed.