Class II major histocompatibility complex (MHC) has tolerance for binding longer antigen peptides than those bound by class I MHC. In this paper, a normal mode analysis on HLA-DR1 class II MHC involving an antigen peptide indicated that the peptide-binding groove had some different dynamic characteristics from that of HLA-A2 class I MHC. The dynamic changes in the class I groove with removal of the bound peptide were limited primarily to the central region and the C-terminal side (corresponding to the C-terminal side of the bound peptide) of the groove, while the dynamic changes in the class II groove with removal of the bound peptide extended to the whole of the groove, and were especially remarkable around a strand located in the N-terminal side (corresponding to the N-terminal side of the bound peptide) of the groove. These results suggest that the N-terminal side of the class II groove is more flexible than the same side of the class I groove, and this flexibility may allow some N-terminal residues of the bound peptide to extend outside the class II groove. Definite anti-correlative motions with removal of the bound peptide appeared between two α-helical regions of class II MHC as in the case of class I MHC. These motions of the class II groove may play an important role in obtaining “a flexible dynamic fit” against diverse longer peptides both of whose terminals extend outside the groove.