Rgs2 (regulator of G-protein signalling 2) gene recently was reported as a quantitative trait gene for anxious behaviour in mice and male Rgs2 knockout mice have been shown to be more anxious than wildtype mice. Therefore we investigated four non-coding single nucleotide polymorphisms in a sample of 173 patients with panic disorder and 173 matched controls of German descent. At the genotype level all four SNPs were associated with panic disorder (p = 0.02-0.05). At the haplotype level the strongest association was observed for a haplotype containing SNP3 and SNP 4 (subgroup men and men with agoraphobia: p = 0.01 and 0.03). This points towards a functional polymorphism at the 3' end of the gene. Our results support the hypothesis that variations of the Rgs2 gene play a role also for the development of anxiety in humans.