Polymorphisms in the organic cation transporter (OCTN) genes SLC22A4 (OCTN1; polymorphism 1672C/T) and SLC22A5 (OCTN2; polymorphism -207G/C) at the inflammatory bowel disease (IBD) 5 locus comprise a two-allele haplotype (SLC22A-TC) associated with increased risk for Crohn's disease (CD). In this study, we examined the contribution of the disease susceptibility haplotype SLC22A-TC to CD in a New Zealand Caucasian population. The frequencies of the gene polymorphisms 1672C/T and -207G/C were examined in 182 patients with CD and 188 ethnically matched controls by PCR-RFLP analysis. There was a significant difference in the allele frequency (0.444 vs 0.519; P = 0.041) of the 1672T polymorphism in the SLC22A4 gene between controls and patients with CD. In contrast, there was no significant difference (0.497 vs 0.552; P = 0.135) for the -207C polymorphism in the SLC22A5 gene. The homozygote SLC22A-TC diplotype was significantly associated with an increased risk for CD (odds ratio 2.19), and the SLC22A-TC haplotype was associated with increased risk (P = 0.0007) of ileocolonic involvement. The population-attributable risk for the SLC22A-TC haplotype is 15.1%. Thus, SLC22A-TC is associated with an increased risk of CD and disease phenotype in our New Zealand CD cohort.