The frequency and distribution of aphidicolin induced and folate sensitive common fragile sites on chromosomes of peripheral blood lymphocytes in untreated non-Hodgkin's lymphoma patients and healthy controls showed a considerable overlap in the expression of common fragile sites between the two groups. However, a significant increase in the expression of 16 aphidicolin induced common fragile sites was seen in untreated lymphoma patients. In the folate deficient cultures only, the common fragile sites 2q22, 8q24, 11q13, 12q21, 16q22, 17p12 and 20p12 were found in both the groups under study. The fragile sites at 8q22, 8q24, 11q13 and 18q21 in patients showed an increased expression over the control group. Interestingly these fragile sites were located in the same chromosomal bands as the oncogenes, MOS, MYC, BCL-1 and BCL-2 as well as cancer breakpoints specifically associated with non-Hodgkin's lymphoma, suggesting the possibility that fragile sites may play a critical role in the pathogenesis of non-Hodgkin's lymphoma.