We have outlined a modified method of DNA extraction from blood and bone marrow that can be used for gene rearrangement studies of leukemia and lymphoma and can consistently give excellent yields of DNA from as little as 1 x 10(6) cells. The method is based on the use of small sample vessels, a marked reduction in solution volume and minimal handling of the specimen. By using known cell numbers from eight leukemic bone marrow samples and four leukemic cell lines, the modified extraction procedure consistently had better yields of DNA, compared with a standard procedure. These findings were confirmed by further comparisons of DNA yields from 14 hypocellular clinical specimens that had been divided into two equal parts for side-by-side DNA extraction with both methods. The quality of the DNA from the modified extraction method was similar to standard methods on subsequent Southern blot analysis and hybridization with immunoglobulin and/or T-cell receptor gene probes. This modified DNA extraction method is a procedure that complements standard extraction methods and expands the number and type of specimens that can be evaluated by the clinical molecular genetics laboratory.