It is generally believed that erythema nodosum is the result of an immunologic attack centered within the subcutaneous fat. This belief, however, is based on indirect evidence. The aim of this study was to analyze whether erythema nodosum could represent an example of a polarized Th1 or Th2 immune response. We have studied herein, by semiquantitative coupled reverse transcription-polymerase chain reaction the Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-10) cytokine gene expression in skin biopsies and peripheral blood from eleven patients with erythema nodosum. As controls, we studied skin and peripheral blood from nine healthy subjects. We found expression of Th1 cytokines in most erythema nodosum skin lesions as well as in their peripheral blood. Both Th1 and Th2 cytokine gene expressions were scarcely or not detected in the skin and peripheral blood of control subjects. These results directly demonstrate that a polarized Th1 immune response occurs in the skin lesions of erythema nodosum patients regardless of the wide variety of provoking agents.