The utility of polymerase-mediated assays in the detection of thet(11;14) involving thebcl-1 major translocation cluster (bcl-1 MTC) was evaluated by analyzing DNA from 33 patients with mantle cell lymphoma, 14 patients with other non-Hodgkin s lymphomas, and five patients with reactive lymphoid hyperplasia. The polymerase chain reaction (PCR) assay was performed using a consensus immunoglobin heavy-chain joining region primer in conjunction with a chromosome 11 specific oligonucleotide primer flanking the translocation site. The sensitivity and specificity of the assay were confirmed by correlation of the (PCR) assay data with restriction analysis. Rearrangements at thebcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis. Amplicons were detectable by PCR in 85% (11 of 13) of the cases shown to bebcl-1 rearranged by restriction analysis. Failure to detect amplification products in DNA samples from non-mantle cell lymphomas and reactive follicular hyperplasia further confirmed the specificity of the assay. Sequential hybridization of the PCR products with oligonucleotide probes 3′ to thebcl-1 MTC primer revealed that the breakpoints in thebcl-1 MTC were clustered around anSstI restriction site over a range of 170 base pairs. The study demonstrates that PCR-mediated assay for the detection of thet(l1;14) at thebcl-1 MTC is specific and sensitive and can be used as an adjunct to restriction analysis in routine diagnostics.