The candidate genes tyrosine hydroxylase (TH) and the dopamine D4 receptor gene (DRD4) are both located in the 11p15.5 region, thus creating strong interest in this region for genetic studies of bipolar affective disorder. It is conceivable that disregulation of the dopamine system could arise from genetic defects in DRD4 or TH, which in turn may lead to susceptibility to this disorder. We have begun our search for an autosomal linkage to bipolar affective disorder in the Old Order Amish (OOA110) with the 48 bp coding region polymorphism for DRD4. A small positive lod score of 1.16 was determined. A new polymerase chain reaction-based tetranucleotide repeat marker for the TH gene was investigated, and also had a small positive lod score of 0.63 at theta = 0.10. This finding replicates the small positive (lod = 0.42) RFLP results of Pakstis et al, (1991a). These two new markers were not able to provide statistically significant results, however their role as modifier genes in the pathogenesis of affective disorders cannot be excluded. Future studies that include the sequence variants within the 48 bp motif of the DRD4 coding region polymorphism, and possibly alternate definitions of the affective disorder phenotype, may provide more definitive answers.