We studied tyrosine hydroxylase (TH) gene variants in mood disorders using linkage disequilibrium techniques. One hundred and forty-five inpatients affected by bipolar (n = 88) and unipolar (n = 57) disorders, and 84 healthy controls, were typed for TH variants using polymerase chain reaction (PCR) amplification. TH was associated with mood disorder, with all affected subjects presenting an excess of TH*2 allele (chi 2 = 8.30, d.f. = 1; P = 0.004) and lack of the TH*1 allele (chi 2 = 6.90, d.f. = 1, P = 0.009). Linkage disequilibrium analyses confirmed the association. Our results suggest a moderate linkage disequilibrium of TH variants with mood disorders.