In order to determine whether or not there are specific chromosomal changes in small cell lung cancer (SCLC), karyotypic analyses of 16 continuous SCLC tissue culture lines, three fresh tumor specimens (bone marrow), one direct preparation of bone marrow involved with SCLC, and two lymphoblastoid lines derived from SCLC patients were studied. Cell lines were derived from primary tumor, or metastases to bone marrow, subcutaneous nodules, or pleural fluid; all 16 lines had biochemical and histologic properties characteristic of SCLC. Of the 15 males and 3 females, 6 patients had no prior treatment. All of the 16 cell lines, the 3 fresh specimens, and the direct bone marrow preparation had a common deletion of the short arm of chromosome #3. Use of the shortest region of overlap analysis showed the common deletion was of the short arm in the regions p(14-23). This specific chromosomal abnormality, del 3p, was not found in five non-SCLC cell lines studied and is of major potential biological and diagnostic importance.