Background: The circulating DNA in plasma/serum of cancer patients has been shown to reflect the characteristics of the tumor DNA including molecular changes, such as rnethylation, point mutations and microsatellite instability. Fragmented nucleosomal DNA in plasma resulting from apoptotic death of the tumor cells may also provide an indication for tumor DNA. In this study, we comparatively analysed plasma DNA methylation and presence of fragmented nucleosomal DNA in patients with lymphoproliferative diseases. Methods: Methylation in the first exon of the tumor supressor gene p16 was investigated by the methylation-sensitive restriction enzyme-related PCR. DNA fragmentation in plasma was analysed by gel electrophoresis. Results: p16 gene methylation was found to occur in 73% of patients but in none of the 20 healthy controls. Nucleosomal DNA fragmentation was detectable in 81% of patients. In 67% of patients, copresence of both parameters was observed. Presence of both parameters a frequent event and may be used as a marker for early diagnosis and during the follow-up of the disease. (C) 2003 Elsevier B.V. All rights reserved.