Recurrent aphthous stomatitis (RAS) is an, ulcerative condition of the mouth, with a polygenic mode of inheritance in which cytokines are thought to play an important role. Ninety-one RAS patients and 91 controls were genotyped for known IL-1A, IL-1B, IL-1RN and IL-6 gene polymorphisms. Inheritance of the G allele of the IL-1B -511 polymorphism was strongly associated with RAS (OR = 2.5, P < 0.00002), with increased numbers of G/G homozygotes (OR = 4.5, P < 0.0005). The G allele of IL-6 -174 also occurred more frequently in RAS (OR = 2.6, P < 0.0001) with greatest risk associated with G/G homozygosity (OR = 3.4, P < 0.0001). IL-1RN VNTR 1/1 homozygotes also occurred more frequently in RAS (OR = 2.0, P < 0.02). Inheritance of the G/G genotype of both IL-1B and IL-6 was a particularly strong predictor for RAS (OR = 8.5).