Background The melanocortin 1 receptor (MC1R) is a highly polymorphic G protein-coupled receptor. Inheritance of various MC1R alleles has been associated with a red hair/fair skin phenotype, increased incidence of skin cancer and altered sensitivity to ultraviolet (UV) radiation. Objectives To investigate whether MC1R genotype influences erythemal sensitivity to psoralen–UVA photochemotherapy (PUVA) in patients with psoriasis and other common skin diseases. Methods Patients (n = 111) about to start PUVA were recruited to the study. Erythemal responses were assessed visually at 72 h and 96 h following PUVA by assessment of the minimal phototoxic dose (MPD). MC1R genotype was determined by direct sequencing. Results Inheritance of the MC1R Arg151Cys allele was associated with a red hair phenotype (odds ratio 25·19, P = 0·0004). In contrast, inheritance of the Val60Leu and Arg163Gln SNPs was associated with increased PUVA erythemal sensitivity (reduced MPD) 72 h following treatment in all patients (n = 111; Val60Leu χ2 = 5·764, P = 0·016; Arg163Gln χ2 = 5·469, P = 0·019) and in a subset of patients with psoriasis (n = 55; Val60Leu χ2 = 4·534, P = 0·033; Arg163Gln χ2 = 7·298, P = 0·007). Inheritance of two or more MC1R SNPs was also associated with increased PUVA erythemal sensitivity (reduced MPD) in both patient groups (n = 111; χ2 = 8·166, P = 0·017; n = 55; χ2 = 10·303, P = 0·016). Conclusions Our data demonstrate that MC1R genotype influences PUVA erythemal sensitivity in patients with psoriasis and other common skin diseases.