Linkage of bipolar (BP) illness with chromosome 18 markers located at 18p11 was recently reported. A possible role for chromosome 18 in the etiology of BP illness was implicated previously by the finding in three unrelated patients of a ring chromosome with breakpoints and deleted segments at 18pter-p11 and 18q23-qter. To test the potential importance of a gene defect on chromosome 18 in our material, we examined linkage with chromosome 18 markers in two families with multiple patients with BP illness or BP spectrum disorders. fourteen simple tandem repeat polymorphisms were used located in the chromosomal region 18p11 to 18q23 and separated by distances of approximately 10 cM on the genetic map. In one family linkage to chromosome 18 could not be excluded. Linkage and segregation analysis in the family suggests that the 12-cM region between D18S51 and D18S61 located at 18q21.33-q23 may contain a candidate gene for BP illness.