Although the precise underlying pathomechanisms of psoriasis have not been fully elucidated, previous reports suggest that T helper 1-type cytokines are critically involved in the pathogenesis of this disease. Interleukin-12 (IL-12), a heterodimeric cytokine, has been suggested to play a major role in the development of T helper 1 cell responses. In this study, the presence of IL-12 mRNA and protein was investigated in normal human skin as well as nonlesional and lesional psoriatic skin. Messenger RNA levels were determined in biopsy specimens by a standard and a nested reverse transcriptase-polymerase chain reaction method. Additionally, IL-12 protein expression was analyzed in situ by immunohistochemistry using an antibody recognizing IL-12 p70. Whereas specific transcripts for IL-12 p35 were reproducibly detected without any significant differences in all samples, enhanced IL-12 p40 mRNA signals were only found in lesional psoriatic skin as compared with normal and nonlesional psoriatic skin. Furthermore, immunoreactivity for IL-12 p70 was markedly increased in the psoriatic skin lesions and was predominantly expressed on mononuclear cells in the dermis. In conclusion, our data suggest a critical role for IL-12 in promoting and maintaining T cell activation and inducing T helper 1-type cytokines such as interferon-gamma in psoriasis. We speculate that IL-12 might be a key cytokine in the pathogenesis of psoriasis.