T-cell responses to heat shock proteins (Hsp) have been suggested to play a role not only in inflammatory conditions, but also in various human autoimmune diseases and in the allograft response. Previous data from our group suggested that during the early posttransplantation (post-Tx) period (<6 months post-Tx), the anti-Hsp60 T-cell repertoires in renal transplant recipients were predominantly proinflammatory. In the later period, they were predominantly regulatory. In agreement with our results, diversification of the T-cell responses toward the carboxy-terminal determinants of Hsp60, related to the resolution of the inflammatory process, was shown in an experimental model of adjuvant arthritis. It has not been clarified whether this diversification is also present in transplantation. In this context, our objective was to analyze cytokine production against autologous Hsp60 peptides from different regions of the protein, using peripheral blood mononuclear cells of 9 renal transplant recipients at 2 timepoints after transplantation: early (<6 months) and late (>1 year). IFN gamma production induced by Hsp60 peptides was observed in 71% and 75% of the patients in the early and late post-Tx periods, respectively. Interleukin (IL)-10 production induced by Hsp60 peptides was observed in 28% of the patients in the early period and in 62% in the late period. Interestingly, the production of IL-10 was induced mainly by peptides of the intermediate and the C-terminal regions. This suggests a predominance of autoreactive regulatory anti-Hsp T-cell repertoire in the late post-Tx period, which predominantly recognize peptides from the intermediate and C-terminal regions of the protein.