This study was undertaken to investigate intracoronary production and systemic release of the atrial natriuretic factor (ANF) and cyclic-guanosine monophosphate (c-GMP) during coronary angioplasty (PTCA). Three coronary blood samples were collected, through a balloon catheter, from the area distal to the lesion: before balloon inflation, at maximum inflation and 5 min later. Four additional venous samples were collected: before PTCA, and 5 min, 2 h and 24 h after the procedure. Local intracoronary c-GMP production increased from the baseline level of 7.5 + 0.9 pmol/ml to 11.1 + 1.3 pmol/ml at maximum balloon inflation (p < 0.01) and decreased 5 min later to 9.5 + 1.0 pmol/ml (p = NS). In contrast, intracoronary ANF production failed to show any significant change at any time during the procedure. Peripheral venous ANF levels increased from 79.1 + 11.1 pmol/ml to 99.9 + 16.6 pmol/ml 5 min after balloon inflation (p < 0.05) and gradually decreased 2 h (91.9 + 13.6 pmol/ml) and 24 h (85.6 + 10.4 pmol/ml) after the procedure. Similarly, peripheral venous c-GMP levels increased from 11.3 + 1.7 pmol/ml before PTCA to 14.9 + 1.9 pmol/ml 5 min after balloon inflation (p < 0.05), and then gradually decreased 2 h (10.8 + 1.4 pmol/ml) and 24 h (8.2 + 1.4 pmol/ml) after the procedure (p < 0.01 and < 0.0001 compared to the peak value, respectively). In conclusion, acute vessel occlusion and distension during balloon inflation stimulates intracoronary c-GMP production without affecting ANF release.