In a study of the direct effects of interferon‐gamma (IFN‐γ) on normal human skin, healthy adult male volunteers received either 3 μg (n=4) or 30 μg (n=9) of recombinant IFN‐γ administered intradermally over 3 days. Biopsies were taken on day 6 and histopathological examination of fixed paraffin‐embedded sections from sites which had received 30 μg IFN‐γ revealed a moderate perivascular lymphohistiocytic dermal infiltrate with mast cells. Immunophenotyping of 5 μm cryostat sections demonstrated that 3 μg IFN‐γ induced keratinocyte HLA‐DR expression in the absence of any significant infiltrate. More intense keratinocyte HLA‐DR expression was produced by 30 μg IFN‐γ in all specimens, with HLA‐DP concurrently expressed in three biopsies. The ratio of CD4:CD8 cells within the infiltrate was approximately 3:1. CD1⁺ cells within the epidermis were markedly depleted by 30μg IFN‐γ, while CD1‐labelled cells were observed in the dermal perivascular infiltrate. Intradermal IFN‐γ induces similar immunopathological changes to those observed in many of the inflammatory dermatoses.