BACKGROUND: Conflicting data exist on the association between functional polymorphisms in the serotonin reuptake transporter (SERT) gene (SLC6A4) and irritable bowel syndrome (IBS). This may be partly because of small participant numbers and varying ethnic origin and sex within the cohorts studied. AIM: To reassess the potential association between the SERT polymorphisms 5-HTTLPR and STin2 in both male and female IBS patients with diarrhoea (IBS-D) and constipation (IBS-C) compared with healthy volunteers. METHODS: In this case-control study, 196 Caucasian Rome II IBS patients [97 IBS-D (aged 18-66 years; 67 female) and 99 IBS-C (aged 18-65 years; 95 female)] and 92 Caucasian healthy volunteers (aged 18-63 years; 60 female) from the UK had genomic DNA extracted from peripheral blood and the 5-HTTLPR and STin2 polymorphisms genotyped. RESULTS: The frequency of the 5-HTTLPR (ss) genotype was slightly lower in both IBS-D (16.5%) and IBS-C (14.3%) patients compared with controls (23.9%), although not significantly (P