In order to assess the possible involvement of thyroid hormone in a human atrial natriuretic peptide (αhANP), we investigated the plasma and urine ANP concentration in patients with primary hyperthyroidism and hypothyroidism. Plasma and urine were extracted through Sep-Pak C₁₈ cartridges and the urine ANP concentration was corrected by urine creatinine (cre. mg/dl) and expressed as fmol/mg·cre. The plasma ANP concentration in patients with untreated hyperthyroidism (32.3±7.0 fmol/ml; n=22) was higher than in normal subjects (p<0.01 vs control; 6.2±0.7 fmol/ml). After restoration to euthyroidism, the plasma ANP concentration (patients with treated hyperthyroidism) fell to normal (8.9±1.9 fmol/ml). The plasma ANP concentration in patients with untreated hypothyroidism (14.1±3.0 fmol/ml; n=7) was higher than normal, but in two of them there was mild renal dysfunction and an incomplete right blundle branch block in the electrocardiogram. It was possible that these factors contributed to the observed increase in plasma ANP. However, a significant positive correlation was found between plasma ANP and free thyroxine (n=40, r = 0.449;p<0.01) and free triiodothyronine (n=40, r=0.546; p<0.01). The urine ANP concentration in patients with untreated hyperthyroidism was markedly higher than in normal subjects (p<0.01), but in untreared hypothyroidism not significantly different from normal.