Chromosomal translocations involving 3q27 are among the most common recurring translocations in non-Hodgkin's lymphoma (NHL) of B-cell phenotype. Molecular cloning of junctional areas of the translocations resulted in isolation of the BCL6 gene adjacent to the breakpoint cluster on 3q27. The gene encodes a zinc-finger transcription factor which is expressed in nuclei of germinal center B-cells. Rearrangement of BCL6 was observed in 6.4 to 14.3% of follicular lymphomas and 28.6 to 35.5% of diffuse large cell lymphomas; regarding the latter, a Japanese series showed a lower incidence. Survival curves suggested that NHL carrying rearrangement of BCL6 and lacking that of BCL2 is curable by chemotherapy. Detailed analysis of the vicinity of translocations showed that the 5' untranslated region of BCL6 was replaced by heterogeneous promoters not only from immunoglobulin genes but also from many previously uncharacterized loci. Bcl-6 protein is expressed in NHL of follicular center B-cell origin, independently of the presence or absence of BCL6 rearrangement. At present, limited information is available about the functional consequences of the rearrangements and, in particular, about their ultimate implications for lymphomagenesis.