The catechol-O-methyltransferase (COMT) val(158)met polymorphism, which codes for the substitution of valine (val) by methionine (met) leading to a reduced COMT activity in homo- or heterozygous individuals, is associated with individual pain sensitivity and dopaminergic responses in Parkinson's disease as well as with various chronic painful diseases. Recent investigations support the notion of an alteration of the medial pain pathway as well as of the descending inhibitory control system in restless legs syndrome (RLS), that both involve dopaminergic transmission as well. Thus, the distribution of the COMT val(158)met polymorphism was assessed in 298 RLS patients and compared with 135 healthy controls in relation to sex, age of onset and family history. The data revealed no significant differences in the distribution of the COMT val(158)met polymorphism in RLS patients compared with the control group, also when the heterozygous and the homozygous group containing the (158)met allele were combined. In addition, sex, age of onset and family history were not associated with the COMT val(158)met polymorphism in this German population of RLS patients. The present study adds to previous mostly negative investigations on the genetic determination of dopaminergic transmission in RLS, which have - so far - only detected an association of the MAO-A activity and RLS in females in a French-Canadian population. Further investigations assessing the different COMT haplotypes and experimental and clinical parameters are nevertheless warranted.