Cells from Burkitt's lymphoma (BL) and from the majority of human B-cell neoplasms show karyotypic changes that characteristically involve chromosomal breakage and recombination in addition to some chromosome gains. These aberrations increase as the tumours progress in vivo, and a similar tendency is seen in BL-derived lymphoid lines in vitro. Epstein-Barr virus (EBV)-transformed lymphoblastoid lines of non-malignant origin also develop karyotypic abnormalities on prolonged culture, but these are predominantly nonrandom gains of whole chromosomes (i.e., non-disjunction events). They have never been observed to acquire the 8;14 translocation, which is an almost constant feature of BL. Nevertheless, there is some concordance between the pattern of chromosome gains found in long-term cultured lymphoblastoid lines and that seen in direct preparations from B-cell neoplasms. Many of the lymphoblastoid lines that have become aneuploid are tumorigenic in immunosuppressed mice, indicating that EBV-transformed human B cells can acquire a malignant phenotype in the absence of specific chromosomal translocations. It is suggested that the predominance of chromosomal breakage and recombination events in the karyotypic evolution of BL and other lymphoid neoplasms comes about because chromosomal instability (which varies within a population) is a major risk factor for lymphoid malignancy, interacting with other risk factors, including impaired T-cell function and EBV to determine the clinical and epidemiological patterns of BI and related neoplasms.