The genetic basis for Graves' disease remains largely unknown, but significant linkage to microsatellite markers on 20q11 suggests that this region harbors a susceptibility gene. One obvious candidate gene at this 20q11 locus is CD40, which encodes a B-cell–surface receptor that is involved in T-cell to B-cell signaling and is implicated in control of T-cell autoreactivity. In addition, an allele of a single nucleotide polymorphism (SNP) in the Kozak consensus sequence of the 5′ untranslated region of CD40 exon 1 has been reported to show modest evidence for association with Graves' disease. We have investigated the role of this 5′ untranslated region (5′ UTR) in Graves' disease susceptibility in our cohort of 451 unrelated white subjects with Graves' disease and 446 healthy controls. The CD40 5′UTR SNP (C → T, position −1) was polymerase chain reaction (PCR)amplified and genotyped using the restriction enzyme NcoI. The frequency of the C allele was 74.8% in Graves' probands compared to 75.1% in controls (not significant [NS]). We find no evidence to support allelic association with Graves' disease at this CD40 SNP, despite the adequate power of the study. We are unable to confirm a role for CD40 in Graves' disease pathogenesis in our U.K. population, however, further studies involving larger patient cohorts and a saturated SNP marker map are required to resolve this issue.