UVB light was used to induce an experimental inflammation in normal human skin in order to investigate its correlation with the activity of the newly described enzyme d-dopachrome tautomerase (DDT) in the fluid of experimental blisters. Macrophage migration inhibitory factor (MIF) activity was determined as a closely related marker of inflammation. DDT and MIF activities were demonstrated in blister fluids in all 10 healthy subjects. All but one of these subjects showed increased activity of DDT and MIF after three minimal erythemal doses (MED) of UVB. The mean activity of DDT increased approximately twofold and the mean activity of MIF also increased twofold after UVB in our experimental model. We found a strong correlation between DDT and MIF activities. The presence of DDT in epidermis and its increase at UV irradiation was confirmed by immunohistochemical studies. In this study, DDT is for the first time demonstrated in the skin. It is also the first time DDT can be related to inflammation, and its covariation with MIF strengthens this observation.