This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 ± 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L ± SEM) rose significantly at the end of balloon deflation (13.4 ± 2.8; p < 0.01) compared with baseline levels (8.8 ± 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 ± 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 ± 0.6) compared with baseline (2.13 ± 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure. Three patients had clinical and angiographic restenosis within 6 months of the angioplasty. These patients had higher levels of IGF-1 and greater IGF-1 release with injection of contrast media. We conclude that regional myocardial ischemia results in release of ANP from the myocardium and a transient increase in lactate concentrations. Total IGF-1 levels do not appear to be altered by ischemia, but this peptide appears to be displaced from the transporter protein by radiographic imaging media. IGF-1 may be a factor in the development of restenosis after angioplasty.