Aims-To determine the changes in serum zinc concentration and the extent of urinary zinc excretion in patients with iron overload receiving the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L(1)) or desferrioxamine (DFX), and to correlate these results with blood glucose concentration. Methods-Serum zinc and ferritin concentrations, urinary zinc and iron excretion were regularly assayed in 39 patients and the glucose tolerance test (GTT) was performed in each patient. Patients were segregated according to their GTT into normal, diabetic, and those with an abnormal GTT. The mean of L(1)- or DFX associated urinary zinc excretion for each group was determined and compared with the other two groups and with normal value. L(1) associated urinary zinc excretion was also compared with L(1) dose, serum ferritin values, and urinary iron excretion. Results-Both DFX and L, were associated with a significantly increased urinary zinc excretion (15.1 (7.3) mu mol/24 hours, 11.1 (6.0) mu mol/24 hours, respectively) compared with normal subjects. In patients receiving DFX this increase only occurred in patients with diabetes mellitus. Both diabetic and non-diabetic patients receiving L(1) treatment excreted more zinc than normal. Diabetic patients receiving L(1) or DFX excreted more zinc than non-diabetics receiving the same treatment. No correlation was found between urinary zinc excretion and L(1) dose or patients' serum ferritin concentrations. In seven patients receiving long term L(1) treatment a fall in serum zinc was observed from an initial 13.6 (1.6) mu mol/l to a final 9.6 (0.8) mu mol/l. In one patient this was associated with symptoms of dry skin and itchy skin patches requiring treatment with oral zinc sulphate. Conclusions-In contrast to DFX, L(1) treatment is associated with increased zinc loss. This, however, is modest and does not lead in most patients to subnormal serum zinc concentrations. In a few patients whose negative zinc balance may give rise to symptoms, zinc supplementation rapidly corrects the deficit.