The amino acid sequences of the variable regions of the heavy chains derived from two idiotypically related human monoclonal rheumatoid factors are reported. The sequences were obtained through automated Edman degradations of the intact, pyroglutamate aminopeptidase cleaved heavy chains and peptides produced from digestion of the pentameric IgM with CNBr. The peptides generated from the CNBr reaction were further digested by trypsin and the Staphylococcus aureus V8 protease. Comparisons of these sequences and those of the light chains from these molecules [Andrews, D. W., & Capra, J. D. (1981) Biochemistry (preceding paper in this issue)] suggest that the idiotypic determinant(s) in this system may reside in the framework portions of these molecules or in their J segments.