Unstable angina occurs most commonly in the setting of atherosclerotic coronary artery disease (CAD), but there is little information concerning the mechanisms responsible for the transition from clinically stable to unstable coronary atherosclerotic plaque. Recently, increased focal infiltration of inflammatory cells into the adventitia of coronary arteries of patients dying suddenly from CAD and activation of circulating neutrophils in patients with unstable angina have been observed. To characterize the presence of inflammation in "active" atherosclerotic lesions, the acute phase reactant C-reactive protein (CRP) was measured in 37 patients admitted to the coronary care unit with unstable angina, 30 patients admitted to the coronary care unit with nonischemic illnesses and 32 patients with stable CAD. CRP levels were significantly elevated (normal less than 0.6 mg/dl) in 90% of the unstable angina group compared to 20% of the coronary care unit group and 13% of the stable angina group. The average CRP values were significantly different (p = 0.001) for the unstable angina group (2.2 +/- 2.9 mg/dl) compared to the coronary care (0.9 +/- 0.7 mg/dl) and stable angina (0.7 +/- 0.2 mg/dl) groups. There was a trend for unstable angina patients with ischemic ST-T-wave abnormalities to have higher CRP values (2.6 +/- 3.4) than those without electrocardiographic changes (1.3 +/- 0.9, p = 0.1). The data demonstrate increased levels of an acute phase reactant in unstable angina. These findings suggest that an inflammatory component in "active" angina may contribute to the susceptibility of these patients to vasospasm and thrombosis.