Macrophage colony-stimulating factor (M-CSF) was recently implicated by in vitro studies as a survival and proliferation factor for Hodgkin/Reed-Sternberg cells. We evaluated pre-treatment serum M-CSF levels in 66 patients with histopathologic diagnosis of classical Hodgkin lymphoma (HL) and looked for possible correlations with baseline clinical characteristics. Significantly higher M-CSF serum concentrations were found in patients with bulky mediastinal mass, systemic symptoms, and elevated ESR but not LDH. There was no significant association between M-CSF level and sex, clinical stage, number of lymph node areas involved, and histopathological subtype of HL. We conclude that serum M-CSF levels are frequently elevated in HL patients and are significantly related to the presence of bulky mediastinal mass and systemic symptoms. These observations may indicate a pathogenetic role of M-CSF in Hodgkin lymphoma.