The frog Xenopus provides a unique model system for studying the evolutionary conservation of the immunological properties of heat shock proteins (hsps). General methods for maintaining and immunizing isogenetic clones of defined MHC genotypes are presented together with more recently developed protocols for exploring hsp-mediated immune responses in vitro (proliferative and cytotoxic assays) and in vivo (adoptive cell transfer and antibody treatment) in adults and in naturally MHC class I-deficient larvae. Finally, techniques to study modalities of expression of the endoplasmic reticulum resident gp96 at the cell surface of tumor and normal lymphocytes are considered.