Psoriasis occurs with at least undiminished frequency in HIV-infected individuals. The behavior of psoriasis in HIV disease is of interest, in terms of pathogenesis and therapy because of the background of profound immunodysregulation. It is paradoxical that, while drugs that target T lymphocytes are effective in psoriasis, the condition should be exacerbated by HIV infection. The etiopathogenesis of psoriasis is unknown, but genetic and environmental factors are thought to be involved. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4+ versus CD8+ T lymphocytes. Current opinion favors an autoimmune basis for psoriasis although the precipitating activating signal(s) within psoriatic plaques remains unknown. Candidate skin autoantigens that have cross-reactive determinants with bacterial antigens include keratins. The immunodysregulation resulting from HIV infection may trigger psoriasis in those genetically predisposed by the Cw*0602 allele. Because CD8 T cells recognize antigen in the context of class I molecules, the identification of a human leucocyte antigen (HLA) class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8+ T lymphocytes in the immunopathogenesis of psoriasis. HLA-Cw*0602 could act as a cross-reactive target for cytotoxic T lymphocytes (CTLs) responding to processed peptides from microorganisms.