Clinical studies have demonstrated that patients with coronary artery disease (CAD) have markers suggestive of increased free radical (FR) activity when compared with normal subjects; however, the relationship between the extent of CAD and level of FR markers is not known. The following indices of FR activity, plasma malondialdehyde (MDA), plasma thiols (PSH), red blood cell (RBC) glutathione (GSH), and RBC superoxide dismutase (SOD) were measured in 58 patients admitted for coronary angiography and in 50 matched controls. Regression analysis demonstrated no significant correlation between MDA, PSH, GSH, or SOD, and the angiographic grade which indicated the severity of the CAD. Patients with angiographically proven CAD (median 7.9 nmol/ml IQR 6.9-9.2) and patients with a history suggestive of angina pectoris but normal coronary angiograms (median 8.4 nmol/ml IQR 7.4-9.9) had significantly raised MDA levels compared with the controls (median 6.85 nmol/ml IQR 6.1-7.4), p < 0.001 and p < 0.005, respectively. The patients with angiographically proven CAD had significantly lower GSH levels (median 1461-mu-M IQR 1348-1709, p < 0.002) compared with the controls (median 1754-mu-M IQR 1492-1930). Significantly raised SOD levels also were detected in patients with angiographically proven CAD (median 121.8 U/ml RBC, IQR 113.8-143.9) and in patients with a history of suggestive of angina pectoris but normal coronary angiograms (median 146 U/ml RBC, IQR 96.8-156.7) when compared with controls (median 96.3 U/ml RBC, IQR 82.4-115.6), p < 0.001 and p < 0.02, respectively. This study provides further evidence indicating abnormalities of FR behavior in CAD but the measurement of MDA, PSH, GSH, and SOD in peripheral venous blood does not allow the presence or severity of CAD to be predicted. This study also reports for the first time the presence of raised MDA and SOD in patients with a history of angina pectoris but normal coronary angiograms; this raises the possibility that abnormal FR activity may be relevant in syndrome X.