We have studied the cutaneous response to ultraviolet radiation, measured objectively as erythema in a sample of 12 body sites on 15 Northern European subjects with multiple doses of ultraviolet B (UVB). Skin pigmentation and the development of photoadaptation in response to five repeated doses of irradiation at three body sites was also measured. We report striking differences of up to 5-fold at different body sites to the same challenge dose (p < 0.001) and demonstrate that for this population, site variation is just as important as between-person variation. Skin color at each body site is a strong predictor of response (p < 0.001) and that this cannot be attributed to vascular differences, but instead we believe it reflects site-specific variations in melanin pigmentation. We also observed similar but smaller within-person effects for responses to another inflammatory agent, dithranol (p < 0.01). Despite this, we did not find evidence for differences in the development of photoadaptation by body site. These results have clear clinical implications for the practice of phototesting prior to commencing phototherapy, for therapeutic failure in sites such as the legs in patients with psoriasis, and perhaps for melanoma body-site distribution.