Equilibrium and nonequilibrium competitive inhibition analyses of a number of antisera to peptide S81 and S82 sequences were carried out through the use of inhibition radioimmunoassays with [125I]S81, [125I]S82, and [125I]S79 and a panel containing 18 related peptides and five myelin basic protein preparations. Two principal determinants were identified, one of them sequential, the other nonsequential. The sequential determinant involved a peptide at or near the C-terminal end of S82 that could be blocked by an interchange of asparagine for glycine at the C terminus. The nonsequential determinant was dominant for a number of rabbit and rat antisera, both anti-S82 and anti-S81, and was shared not only by S81 and S82 but also by S8 and S80, i.e., the family of residues of bovine MBP sequence 69-83. Neither determinant was expressed in any of the myelin basic protein preparations, and the nonsequential determinant was not expressed in peptide sequences smaller than S8.