Macrophage migration inhibitory factor (MIF), an important pro-inflammatory cytokine, is over-expressed in plaques of psoriasis and increased levels are found in the sera of patients with psoriasis. Promoter polymorphisms of the MIF gene are associated with increased production of MIF and have been found to confer increased risk of susceptibility to chronic inflammatory diseases. We investigated whether there is an association between promoter polymorphisms of the MIF gene and chronic plaque psoriasis. Two hundred and twenty-eight UK caucasian patients with chronic plaque psoriasis, and a control panel of 401 UK caucasian normal volunteers were studied. MIF promoter polymorphisms were genotyped by allelic discrimination, or by a fluorescently labeled primer method, and capillary gel electrophoresis. Carriage of either the MIF-173*C polymorphism or the MIF CATT(7) polymorphism was positively correlated with psoriasis (odds ratios (OR) 1.52 95% confidence intervals (CI) 1.05-2.19 (p=0.024) and OR 1.67 95% CI 1.1-2.5 (p=0.013), respectively. The OR for presence of the CATT(7)-MIF-173(*)C haplotype versus all other haplotypes combined was 1.69 95% CI 1.2-2.5 (p=0.008). The results provide evidence for polymorphisms in the MIF gene, and in particular the CATT(7)-MIF-173(*)C haplotype, being of importance in susceptibility to psoriasis.