This study evaluated the diagnostic value of C-reactive protein (CRP) combined with a clinical decision rule in the exclusion of pulmonary embolism (PE) and compared this with D-dimer. In 363 consecutive outpatients CRP and D-dimer test were performed and clinical probability of PE was assessed. Patients with D-dimer levels<500 microg/l and clinical probability indicating 'PE unlikely' were followed for 3 months. Ventilation-perfusion scan or spiral computerized tomography was performed in patients with D-dimer levels>or=500 microg/l or clinical probability indicating 'PE likely'. The CRP had a sensitivity of 95.7% [95% confidence interval (CI): 90-100] and negative predictive value (NPV) of 98.4% (96-100). CRP<5 mg/l with clinical probability score indicating 'PE unlikely' (n=108, 30%), had a sensitivity of 96.7% (90-100), a specificity of 43.0% (37-49) and NPV of 99.1% (97-100). D-dimer<500 microg/l with clinical probability score indicating 'PE unlikely' (n=170, 51%), had a sensitivity of 96.7% (90-100), a specificity of 67.9% (62-74) and NPV of 99.4% (98-100). Based on retrospective data it was concluded that a standard CRP test can potentially be used to safely exclude PE, either as a sole test or combined with clinical probability assessment. Prospective studies are needed to confirm these findings.