The effects of secondary hyperparathyroidism (sHPTH) on immunoreactive insulin (IRI) release and glucose (G) tolerance were studied in two groups of dialysis patients with normal (NPTH, n = 9) or elevated PTH levels (HPTH, n = 8), 27 +/- 24 and 660 +/- 440 pg/ml, respectively. The patients received an intravenous glucose tolerance test (IVGTT) using 0.33 g/kg of glucose solution. G, IRI and C-peptide (C-p) levels were determined calculating the G constant decay (K) and the relative incremental areas for each study. Regardless of PTH levels, all patients showed an impaired glucose tolerance (GT). IRI secretion and K values were not significantly different between the two groups. However, a significantly lower K value with a reduced (although not significant) early and late IRI secretion was found in the subgroup of patients with more severe. sHPTH (PTH: 560-1,500 pg/ml, n = 5) as compared to patients with moderate sHPTH (PTH: 87-341 pg/ml, n = 4) or normal (5-32 pg/ml, n = 8) PTH levels. No relationship was found between PTH and G, IRI or C-p levels. Our results point to a threshold limit for PTH's inhibitory effect on IRI secretion and suggest that other factors, known to affect IRI secretion and GT besides PTH levels, may modulate the role played by excess PTH levels on carbohydrate metabolism of dialysis patients.