We have compared the value of immunohistochemical and polymerase chain reaction (PCR) techniques in distinguishing follicular lymphoma from follicular hyperplasia in formalin-fixed paraffin-embedded tissues of 41 follicular lymphomas, 15 reactive lymph nodes and 5 reactive tonsils. Immunohistochemistry demonstrated bcl-2 protein in the follicle centre cells of 97% of follicular lymphomas whereas monoclonal immunoglobulin light chain was detected in 83% of cases. Assessing the lowest proliferating follicle of each case by MIB-1 immunostaining, proliferation fractions in the lymphomas varied from 0.5% to 59% (mean 15.6%). Over 80% of lymphomas had proliferation fractions of less than 25%. PCR detected gene rearrangement either at the bcl-2 locus, or at the IgH locus, or at both loci in 32%, 44% and 61% of lymphomas, respectively. The follicle centre cells of the reactive lymph nodes and tonsils were all bcl-2 protein negative and polytypic for kappa and lambda light chains. Proliferation fractions of the lowest proliferating follicle in each reactive case ranged from 30.5% to 86.8% (mean 64.9%). Rearrangements of the bcl-2 or IgH loci were not detected in any reactive case. This study demonstrates that bcl-2 and light chain immunostaining are the most consistently helpful aids to diagnosing follicular lymphoma. A low proliferation fraction also indicates lymphoma but a high proliferation fraction does not exclude the diagnosis. Immunostaining with a combination of anti bcl-2 and MIB 1 antibodies is a sensitive and specific method for identifying follicular lymphoma, is technically simple to perform and easy to interpret. In occasional cases, where immunostaining gives equivocal results, PCR analysis can confirm lymphoma, but a negative result does not exclude the diagnosis.