An allergenically active protein preparation isolated from normal human dandruff has been subjected to immunological analysis by immunoelectrophoretic and gel-diffusion studies using both homologous rabbit antisera and rabbit antisera against human blood proteins. Human dandruff extracts used in allergy practice contain [gamma]-globulin, [gamma]2-glycoproteins and serum albumin the precipitation patterns in agar indicate these serum proteins to be partially denatured. The [gamma]2-glycoproteins and the albumin retained in the most active allergen preparation share antigenic determinants with some of the other protein constituents; inhibition studies indicate (N-glycosidic) lysl-eugar units to be involved. The [gamma]2-glycoproteins belong to the 2.5 S class, and a study of the cross-reaction of anti human dandruff serum with horse dandruff protein leads to the conclusion that cross-precipitation is most likely due to shared lysl-sugar determinants incorporated in the respective 2.5 S [gamma]2-glycoproteins. Human sweat contained many of the proteins encountered in dandruff extracts. The possible etiological significance of the dandruff allergen(s) in human atopic disease is discussed.