Interleukin-6 is involved in T-cell activation and possibly plays a role in the pathogenesis of acute rejection of transplanted organs. This is indicated by elevated levels of interleukin-6 in serum and urine of renal allograft recipients, and elevated amounts of mRNA for interleukin-6 in all different cell types of the renal allograft during acute rejection episodes. However, transplant recipients receive immunosuppressive drug therapy which may inhibit production of interleukin-6 at the post-transcriptional level. Therefore, the aim of the present study was to detect interleukin-6 in biopsies taken during acute renal allograft rejection by immunohistochemical staining. In addition, serial sections were stained with cellular markers to identify interleukin-6-producing cells. In biopsies taken during acute rejection (n = 7), interleukin-6 could be detected in tubular cells (7/7) mesangial cells (3/7) and monocytes/macrophages (4/7), but not in vascular endothelium or lymphocytes. In control biopsies weak interleukin-6 staining of tubular cells only was present or there was no staining at all. We conclude that interleukin-6 is actually produced in the renal allograft during acute rejection, and that elevated urinary interleukin-6 levels during acute rejection seem to originate mainly from synthesis of interleukin-6 by renal tubular cells.