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Evidence is presented for two populations of Ia-like molecules on the human B cell line Raji. Two monoclonal antibodies, L203 and L227, are described. Both recognize nonpolymorphic determinants on B cell antigens. Both immunoprecipitate 34,000- and 28,000-dalton material from 125I-labeled extracts of Raji, but L227 precipitates 25,000-dalton material as well. Immunodepletion experiments confirm that the antibodies react with two different populations of molecules.