An index of the activation of NADPH-oxidase in the production of free radicals is CO2 production by the hexose monophosphate shunt of polymorphonuclear cells (PMN). 14CO2 production from glucose-1-C14 was studied as an indicator of PMN function after addition of latex or zymosan to predialysis whole blood, and correlated with the years spent on hemodialysis. In a series of 49 patients, a nadir in PMN metabolic activity, when compared with healthy controls, was reached in a subgroup treated for less than 24 months (n = 24, latex: 109.5 +/- 10.1 vs. 233.7 +/- 11.8; zymosan: 181.9 +/- 18.9 vs. 407.8 +/- 19.3 DPM/10(3) PMNs; p less than 0.01). In patients treated by dialysis for longer than 24 months, PMN metabolic function was significantly better, resulting in partial correction of the defect for both latex and zymosan. Phagocyte CO2 production in response to latex or zymosan correlated significantly with years of dialysis treatment (r = 0.63 and 0.56, respectively, n = 49; p less than 0.001). These findings may have implications for phagocyte reactivity towards infection, bioincompatible dialyzer membranes, and renal transplantation.