Macrophages and T lymphocytes accumulate and are activated in atherosclerotic plaques. We tested the hypothesis that plasma levels of the monocyte/macrophage and T-lymphocyte activation markers, monocyte chemoattractant protein-1 (MCP-1) and soluble interleukin-2 receptor (sIL-2r), respectively, can be used in acute coronary syndrome classification and risk prediction. Blood samples were collected at hospital admissions of 183 patients who had ischemic chest pain. Of these, 59 had acute myocardial infarction, 60 had unstable angina, and 64 had angina pectoris. No significant differences in the levels or proportions of subjects with increased levels of MCP-1 or sIL-2r were found across groups. During a mean follow-up of 13 months, 117 patients (64%) had a study end point (i.e., cardiac death, recurrent myocardial infarction, unstable angina, or revascularization). Increased levels (above median) of MCP-1 and sIL-2r were associated with increased risk, with odds ratios of 1.85 (95% confidence interval 0.92 to 3.73, p = 0.08) and 2.34 (95% confidence interval 1.16 to 4.71, p <0.02), respectively. In summary, in this unselected patient population with a very high rate of coronary events during follow-up, increased plasma levels of MCP-1 and sIL-2r were helpful for predicting new coronary events.