Studies on immunoglobulin gene rearrangement in lymphoid lesions are an increasingly important application of molecular biology in diagnostic medicine. The authors have therefore examined the possibility of detecting such rearrangements in formalin-fixed, paraffin-embedded pathology specimens. Southern blots of DNA obtained from optimally fixed tissues were very similar to blots of unfixed material, except that the electrophoretic mobility of the fixed DNA fragments was sometimes slightly reduced. High-molecular-weight DNA was not recovered from suboptimally fixed partially autolysed samples. Increasing the time of exposure to formalin resulted in loss of hybridizable DNA. Monoclonal rearrangements of heavy and light chain immunoglobulin genes could be detected in formalin-fixed specimens provided that these fixation artifacts were taken into consideration. This technique expands the pool of material available for studies on gene rearrangement and should facilitate the use of such studies in clinical medicine.