OBJECTIVE: The loudness dependence of auditory evoked potentials (LDAEP) provides a measure of the central serotonergic activity. As dopamine transporter availabilities also correlate with LDAEP, a dopaminergic influence is probable. The enzyme catechol-O-methyltransferase (COMT) is involved in the inactivation of synaptic dopamine. The aim of this study was to investigate the relationship between genetic variants of the COMT gene influencing synaptic dopamine levels and the LDAEP. METHODS: Rs737865 in intron 1, rs4680 coding for a Val158Met substitution and rs165599 in the 3' region were investigated in 95 carefully selected healthy subjects of German descent (41 males, 54 females). The LDAEP was calculated as a linear regression slope with stimulus intensity as independent and N1/P2-amplitude as dependent variables. RESULTS: Single marker analysis showed weak associations for two single nucleotide polymorphisms (SNPs) (rs737865: CC vs. T allele carrier; rs4680: G-allele carrier vs. AA homozygotes). A-G (rs4680-rs165599) was associated with lower LDAEP scores. Accordingly, haplotype analysis with all SNPs (rs737865-rs4680-rs165599) showed that the T-A-G haplotype was associated with lower scores. CONCLUSIONS: These findings support the hypothesis that the LDAEP is also influenced by dopaminergic transmission. However, replications of these very preliminary but potentially important findings in independent samples are needed.