11 cultured human melanoma cell lines were tested for the expression of DR antigens by using specific allo- and xenoantisera in an indirect rosette microassay. Four of these melanoma cell lines expressed DR antigens, but in lower amounts than expressed on cultured human B-lymphoid cells. Rabbits injected with the DR-positive melanoma cells produced antibodies that were serologically and immunochemically reactive with B-cell-derived DR antigens. Immunochemical studies indicate that melanoma cell-derived DR antigens have a two-chain structure with 34,000 and 27,000 mol wt components. The melanoma cell-derived DR beta-chain at 27,000 mol wt is slightly smaller than that of the Victor cell DR beta-chain whose mol wt is 29,000.