Class II histocompatibility antigens from a homozygous human lymphoblastoid B cell line (HLA-A3,3; B7,7; Dw2,2; DR2,2; MT1,1; DC1,1; MB1,1) were isolated by an exclusively chemical procedure. After the separation of the alpha and beta chains the amino acid sequences of the extracellular parts of the DR2 alpha and the DR2 beta chains could be determined, in spite of the heterogeneity of both fractions. Peptides isolated in considerably lower yields indicated at least one more alpha chain and 6 further beta chains. By the investigation of these lower-yield enzymatic fragments, in addition to the DR2 alpha and DR2 beta chains, we can now report on the partial amino acid sequences of a DC alpha chain, a second beta chain of DR type and one beta chain of DC type. Furthermore, the isolation of a characteristic glycopeptide suggests the existence of a second beta chain of DC type. The following class II antigens are therefore identified: DR2 alpha/DR2 beta 1, DR2 alpha/DR2 beta 2, DC1 alpha/DC1 beta 1, DC1 alpha/DC1 beta 2, indicating that each subclass can be subdivided into two antigens because each alpha chain type can associate with at least either beta 1 or beta 2. Further investigations must clarify whether the remaining three beta chains are of the DR, DC, or of a third beta chain type. Amino acid sequence comparisons confirm that the human DR antigens are the equivalent of mouse I-E antigens, while human DC antigens are the equivalent of mouse I-A antigens.