Twenty-one cases of mucosa-associated lymphoid tissue (MALT) lesions have been analyzed by Southern blot for immunoglobulin heavy chain (IgH) and T-cell receptor beta chain (TcR beta) gene rearrangements (GR). The sites included colon, stomach, liver, nasopharynx, salivary and lacrimal gland, conjunctiva, tonsil, breast, and lung. Two of the lesions (parotid and conjunctiva) were malignant lymphomas and one case showed lymphoproliferative disorder. In the cases of malignant lymphomas, IgH GR were detected, and in the case of lymphoproliferative disorder, both IgH and TcR beta genes were rearranged. Among the remaining 18 cases, 9 showed inflammatory infiltrate, 3 lymphoid hyperplasia, 3 atypical lymphoid hyperplasia, 1 carcinoma of the tonsil, 1 breast carcinoma, and one was a sample of normal Peyer's patches. Among these 18 cases, 3 showed TcR beta GR, 6 showed double IgH and TcR beta GR, and 4 IgH GR. Often multiple rearranged bands were observed, composing 10-30% of the total DNA analyzed. The control tissue (Peyer's patches) showed no GR. Because IgH and TcR beta GR are used to determine monoclonal proliferations of T and B lymphocytes, which occur in malignant lymphomas, it is vital to determine the specificity of such a test. This report stresses the fact that in MALT lesions false-positive results are not uncommon and therefore the results of IgH and TcR beta GR studies have to be interpreted with caution. The presence of multiple GR in the inflammatory lesions indicates proliferation of minor monoclonal populations that can be detected with the use of Southern blot technology.