Very few studies have investigated linkage between manic depressive illness and markers from chromosome 20. Apparently no cytogenetic abnormalities involving chromosome 20 have been described in patients with affective disorders. Several interesting candidate genes of possible psychiatric relevance have been mapped to chromosome 20, including genes encoding a G-protein subunit and two enzymes involved in the phosphatidylinositol cycle, which have been implicated in the pathophysiology of affective disorder as well as the action of lithium, and two alpha-adrenergic receptors. The present study investigated linkage between manic depressive illness and 11 markers from chromosome 20 in two manic depressive families, and did not find evidence for a major disease allele. A single microsatellite marker, D20S39, yielded positive lod scores or all models in each family in the two-point affecteds-only analyses. However, this was not supported by two-point analyses with flanking markers or multi-point affecteds-only analyses. No evidence of linkage between manic depressive illness and markers covering chromosome 20 was found assuming dominant or recessive mode of inheritance.