Polymorphic light eruption (PLE) is a common skin disease, susceptibility to which is genetically determined. The prevalence of PLE is significantly increased in patients with lupus erythematosus (LE) including subacute cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE), which may reflect a common genetic background. Experimental evidence supports a role for reactive oxygen species (ROS) in the pathogenesis of PLE, and the family of glutathione-S-transferase (GST) enzymes exerts a critical physiological role in cellular protection against this oxidative damage. Our aim was to look for association between the functional GST gene polymorphisms and PLE, SCLE, and DLE in a case-control study. The carrier frequency of GSTP1 Val(105) in subjects with PLE was 40%, significantly lower than the carrier frequency in controls (54%, P=0.019), although significance was lost on correction for multiple testing. However, the carrier frequency of the GSTP1 Val(105) allele in combined cutaneous LE (SCLE and DLE) patients with PLE was 42%, significantly lower than in those without PLE (72%), which did survive correction (corrected P=0.043). We have identified evidence supporting a protective GSTP1 allele, the first genetic association to be reported for PLE. This supports a role for ROS in the pathogenesis of PLE and may provide a therapeutic target for future treatment of this common, often disabling, condition.