We studied the effect of parathyroid hormone (PTH) on the proliferation of T cells from patients with end-stage renal disease (ESRD) (n = 16) and normal subjects (n = 20). In patients with ESRD, T-cell proliferation expressed as stimulation index (SI) was significantly decreased from 99.2 +/- 31.2 to 46.3 +/- 10.8, when 10 ng/ml of recombinant PTH (rPTH) was added in vitro. The reduction of SI with rPTH was dose dependent. However, in normal subjects, the SI was increased from 56.2 +/- 13.6 to 67.9 +/- 16.5 (p < 0.01) by addition of rPTH. These findings were also shown by allo or specific antigen-induced T-cell stimulation. When T cells from normal subjects were pretreated with 10 ng/ml of PTH, with 100 mg/dl of urea or with a condition of pH 7.0, the effect of rPTH was changed to decrease the T-cell proliferation induced by anti-CD3 antibody. These data suggested that uremic state, including hyperparathyroidism, changed the response of T cells against PTH.