SUMMARYWith indirect immunofluorescence techniques we demonstrated that recombinant gamma‐interferon induced the expression of the class II antigens HLA‐DR and HLA‐DQ as well as intercellular adhesion molecule‐1 (ICAM‐1) on normal, cultured human keratinocytes grown in low‐calcium, serum‐free medium. Each antigen displayed a distinctive cellular staining pattern. HLA‐DR was strongly localized to perinuclear zones with intense cell surface expression; HLA‐DQ displayed a perinuclear accentuation, but with minimal cell surface staining, and ICAM‐1 was strongly expressed in a diffuse cytoplasmic pattern with intense cell surface expression. Keratinocytes grown in medium supplemented with 10% fetal calf serum underwent differentiation, with a diminished expression of all three antigens as compared to those grown in low‐calcium, serum‐free medium.These results confirm that gamma interferon can differentially regulate HLA‐DR nd HLA‐DQ expression; that there are probably different biochemical metabolic pathways by which these three molecules are expressed on keratinocytes, and that the expression is also a function of the degree of keratinocyte differentiation. The strong cell surface expression of ICAM‐1 is suggested to be of major importance as the recognition molecule, by which T cells bind to gamma interferon exposed keratinocytes, and suggests and integral role for this molecule in epi