We investigated total copper (Cu++) and zinc (Zn++) content in plasma and peripheral blood mononuclear cells (PBMC) and its impact on proliferative ability of the latter in patients on chronic hemodialysis versus age- and sex-matched healthy volunteers, plasma levels of CU++ and Zn++ were significantly lower in dialysis patients compared with the control group (83.6 +/- 7.29 v 95.1 +/- 9.63 mug/dL, P < .03 for Cu++; 71.1 +/- 7.64 v 89.7 +/- 12.55 <mu>g/dL, P < .005 for Zn++). Basal total PBMC-associated Cu++ content was significantly higher in uremic patients (19.3 +/- 3.59 v 14.6 +/- 2.72 <mu>mol/mg protein, P < .005). Basal PBMC-associated Zn++ concentration was also significantly elevated in hemodialysis patients compared with their healthy counterparts (23.9 +/- 5.64 v 10.5 +/- 2.64 <mu>mol/mg protein, P < .005). In addition, we incubated PBMC of the uremic patients versus healthy control PBMC in a Zn++-free versus Zn++-enriched medium. After a 72-hour incubation, total cell-associated Zn++ of both normal and uremic cell populations increased significantly compared with the respective baselines (34.6 +/- 22.49 v 4.3 +/- 1.42 and 20.3 +/- 10.71 v 5.8 +/- 2.22 <mu>mol/mg protein, respectively). However, no statistically significant difference was evident between the 2 groups (34.6 +/- 22.49 v 20 +/- 10.7 mu mol/mg protein). Total cell Zn++ content, on the other hand, was significantly increased in uremic PBMC after 72 hours of incubation in Zn's-enriched medium compared with the control group (63.3 +/- 26.12 v 18.6 +/- 13.42 mu mol/mg protein, P < .005). A significant increase in PBMC proliferation evaluated by SH-thymidine incorporation was evident in the Zn++ enriched culture (35,559 +/- 4,136 counts per minute [CPM] v 20,497 +/- 7,263 CPM, P < .005). Cu++ enrichment of the medium, while resulting in a modest elevation of cell-associated Cu++, did not produce such a proliferative effect. Copyright (C) 2001 by W.B. Saunders Company.