Despite significant advances in treatment, the aetiology of Hodgkin's disease has remained elusive. While epidemiology has uncovered the likely infectious nature of the malignancy, neither the causative agent nor the cell of origin have been identified. The available epidemiological, histological and molecular biological evidence were reviewed and the following conclusions reached. Hodgkin's disease is probably an infectious, but not contagious disease, and is compounded by immunodeficiency. The suspected role of the Epstein-Barr virus (EBV) as causative agent has been substantially weakened, although a role as co-factor is likely. A prime candidate for the cell of origin seems the interdigitating reticulum cell (IRC). Reed-Sternberg cells found in patients with Hodgkin's disease may represent in vivo hybridomas of the IRC with B- and/or T-cells. As IRC is unlikely to be susceptible to EBV, a retrovirus may be the culprit. Hybridomas may be formed when retroviral antigens expressed by a macrophage cell attract reactive B- and T-cells and, instead of an immune reaction, fusion occurs. Further research is necessary in the search for the causative agent of Hodgkin's disease.