PURPOSE: In patients with lymphoma, we investigated the impact of contrast-enhanced CT on PET attenuation correction in lesions and normal tissues, particularly when PET/CT was performed after chemotherapy. METHODS: Fifty patients (51+/-18 years) with Hodgkin's disease (n=17) or non-Hodgkin lymphomas (n=33) were studied before and after chemotherapy. PET/CT scans were performed 60 min after injection of FDG. Iopamiron 300 (iopamidol, 1.5 cc/kg) was injected immediately afterwards, followed 50 s later by a second craniocaudal CT (CT+). PET images were successively reconstructed using the unenhanced CT (PET-) and the CT+ (PET+) for attenuation correction, using iterative reconstruction (4 iterations, 8 subsets, 5 mm post-filtering). HU(mean), SUV(max) and SUV(mean) were measured before and after chemotherapy in ten non-tumoural ROIs [aorta, femur, kidney, lung, iliopsoas muscle, occipital cortex, T12 vertebra, liver, spleen and inferior vena cava (IVC)] and in tumoural lymphadenopathies or malignant tissues (n=397 and 51 VOIs respectively before and after chemotherapy) using a 3D-thresholding method (identical threshold for PET- and PET+). ROIs were defined on the PET- and automatically applied on the unenhanced CT (CT-), the CT+ and the PET+. RESULTS: In the non-tumoural tissues, HU(mean) increased significantly in the CT+ compared with the CT- in the vessels and the highly vascularised organs, and slight increases were observed in the occipital cortex (+11%), the iliopsoas muscle (+6%) and the femur (+3%). SUV(max) increased significantly in the PET+ compared with the PET- in the aorta (+14%), the liver (+10%), the spleen (+10%) and the IVC (+12%). SUV(mean) increased significantly in the PET+ compared with the PET- in the aorta (+15%), the kidney (+13%), the liver (+11%), the spleen (10%) and the IVC (+12%). In the lesions, HU(mean) was not significantly different before and after chemotherapy, whatever the normal region considered. SUV(max) increased significantly after treatment in the T12 vertebra (+12%). SUV(mean) increased significantly after treatment in the T12 vertebra (+13%) and in the liver (+12%). HU(mean) increased significantly in the CT+ compared with the CT- in the lesions (+55%) before chemotherapy. SUV(max) and SUV(mean) increased significantly in the PET+ compared with the PET- in the lesions (+4%) only before chemotherapy. No significant difference was seen in measurements (HU(mean), SUV(max) and SUV(mean)) after chemotherapy. CONCLUSION: Our study demonstrates that use of enhanced CT for attenuation correction has a negligible effect on quantification at staging and after chemotherapy. A "single-shot" enhanced PET/CT may thus be performed in the evaluation of patients with lymphoma at staging, during treatment and at follow-up.