The hypothesis implicating the serotonergic system in the pathophysiology of obsessive-compulsive disorder (OCD) is supported by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). Since SSRIs act on the serotonin transporter (5-HTT), it has been suggested that the 5-HTT gene (SCL6A4) could be a good candidate for OCD. The SCL6A4 gene has a 44-bp insertion/deletion polymorphism in its promoter region (5-HTTLPR). Previous studies have revealed an association between OCD and the l allele. We analysed the 5-HTTLPR polymorphic system in 115 Mexican OCD patients and 136 controls. No significant association was found between l allele and OCD (chi2 = 1.54, d.f. = 1, p = 0.21). Furthermore, we assessed alternative methods that employ family-based designs in a sample of 43 trios. Haplotype-based haplotype relative risk and transmission disequilibrium analysis did not show a preferential transmission of l allele to OCD probands. Our results indicate the need to analyse larger samples using family-based methods.