The presence of donor-specific alloreactive helper and cytotoxic T cells has been described in allograft biopsies obtained from individuals undergoing acute allograft rejection of various solid organs. However, not all of these lymphocytes demonstrated specificity to mismatched donor HLA antigens. The identity of the antigens to which these T cells are directed to is still unknown at present. The possibility that heat shock proteins (Hsp) could serve as antigenic determinants to which these T cells respond has been raised. We have recently cloned and characterized a novel Hsp of 45Kd molecular weight. In the present study we show that the synthesis of this Hsp (HDJ-2) as well as Hsp60 is significantly elevated in kidney biopsies from individuals undergoing acute and chronic rejection. No message was detected either for HDJ-2 or Hsp60 in biopsies obtained from normal pretransplant kidneys or posttransplant kidneys with no rejection. However, there was some increase in Hsp in miscellaneous causes of allograft dysfunction such as infection and drug allergy. But, this was not as consistent as that noted for allograft rejection. This marked increase in Hsp expression during allograft rejection suggests Hsps as potential candidates for antigenic determinants contributing to kidney rejection.