The plasma concentration of pancreatic polypeptide (PP-like immunoreactivity) was measured in different vascular beds in order to determine regional kinetics of endogenous PP in fasting, supine subjects with normal or moderately decreased kidney function. Patients with kidney disease (n = 10) had a significantly higher level of circulating PP than controls (n = 10): median PP = 52 (range 21 to 352) v 20 (6 to 143) pmol/L, respectively (P less than 0.02). Circulating PP was inversely correlated to 51Cr-EDTA plasma clearance (r = -0.57, P less than 0.02, n = 14) and directly correlated to serum creatinine concentration (r = 0.70, P less than 0.01). Hepatic venous PP was significantly higher than systemic PP in both controls and patients with kidney disease (P less than 0.001, n = 15). The values were positively correlated (r = 0.98, P less than 0.001; slope = 1.37 +/- 0.05, P less than 0.001), indicating a progressively increasing rate of PP secretion in subjects with raised circulating PP. No statistically significant difference could be detected between systemic and renal venous PP or across the lung, left adrenal gland, or lower limb. Assuming steady state between secretion and biodegradation, the metabolic clearance rate of the peptide was estimated to be approximately 600 to 800 mL/min in controls and slightly below this value in patients with nephropathy. These results suggest that the raised circulating PP found in patients with decreased kidney function is due to both increased secretion and decreased degradation.(ABSTRACT TRUNCATED AT 250 WORDS)