Recombinant DNA techniques to detect the rearrangement of genes encoding immunoglobulins and T-cell-antigen receptors have been used to identify clonality in lymphoid lesions. To determine the utility of such techniques in cytologic specimens, DNA was analyzed in 24 effusions and 6 fine needle aspirates. Immunophenotypic studies were also performed on the 19 specimens with suspected hematopoietic malignancies. Sufficient material for DNA analysis was present in 28 of the 30 specimens. Immunoglobulin or T-cell-receptor gene rearrangement was present in 13 specimens with atypical cytologic findings; DNA studies provided more information than did the immunologic studies in 3 cases. One T-cell malignancy showed T-cell receptor and heavy-chain gene rearrangement, and one B-cell malignancy showed immunoglobulin and T-cell receptor gene rearrangement. In all patients except one with no evidence of gene rearrangement, the morphologic and immunologic studies also favored a reactive process. Control specimens showed a germline configuration. This study demonstrated that DNA gene rearrangement studies are feasible on many cytologic specimens and may be useful in diagnostically difficult cases.