GABAergic systems have been implicated in the pathogenesis of anxiety, depression and insomnia. These symptoms are part of the core and comorbid psychiatric disturbances in post-traumatic stress disorder (PTSD). In a sample of Caucasian male PTSD patients, dinucleotide repeat polymorphisms of the GABA(A) receptor beta 3 subunit gene were compared to scores on the General Health Questionnaire-28 (GHQ). As the major allele at this gene locus (GABRB3) was G1, the alleles were divided into G1 and non-G1 groups. On the total score of the GHQ, which comprises the somatic symptoms, anxiety/insomnia, social dysfunction and depression subscales, patients with the G1 non-G1 genotype had a significantly higher score when compared to either the G1G1 genotype (alpha=0.01) or the non-G1 non-G1 genotype (alpha=0.05). No significant difference was found between the G1G1 and non-G1 non-G1 genotypes. When the G1 non-G1 heterozygotes were compared to the combined G1G1 and non-G1 non-G1 homozygotes, a significantly higher total GHQ score was found in the heterozygotes (P=0.002). These observations suggest a heterosis effect. Further analysis of GHQ subscale scores showed that heterozygotes compared to the combined homozygotes had higher scores on the somatic symptoms (P=0.006), anxiety/insomnia (P=0.003), social dysfunction (P=0.054) and depression (P=0.004) subscales. In conclusion, the present study indicates that in a population of PTSD patients, heterozygosity of the GABRB3 major (G1) allele confers higher levels of somatic symptoms, anxiety/insomnia, social dysfunction and depression than found in homozygosity.