Serum unbound free fatty acid levels (FFAu) were measured in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) using the fluorescent probe acrylodan intestinal fatty acid binding protein (ADIFAB). These are the first measurements of FFAu under nonphysiologic conditions. In these studies, FFAu levels were determined in 22 patients 5 minutes before and 30 minutes after the procedure. Post-PTCA FFAu levels were higher than pre-PTCA levels in all patients. The average post-PTCA level for all patients was 103 nM, about 14-fold higher than the 7.5 nM value observed in healthy subjects. Although all patients exhibited elevated FFAu levels after PTCA, ischemic ST-segment changes were observed in only 11 of these patients. The average post-PTCA FFAu levels for patients with significant ST-segment changes (123 nM) were significantly higher than those in patients who did not exhibit such changes (47 nM). Average FFAu (22 nM) levels before the procedure were elevated in the patient population relative to healthy subjects and these values correlated positively with post-PTCA levels. These results suggest that increased serum FFAu levels reflect angioplasty-induced ischemia and that FFAu levels may provide a more sensitive measure of ischemia than electrocardiographic measurements. Moreover, because 30% of these patients had post-PTCA FFAu concentrations exceeding those found to alter in vitro cell function, the increased serum FFAu levels that accompany ischemia may be deleterious for myocardial function.