Cytogenetic analyses of 40 confirmed malignant mesotheliomas (MMs) are reported. Pleural effusion cells were studied in 90% of the cases by direct method or after culture or both. Biopsy and ascites fluid were also analyzed in some patients. A normal karyotype was found in nine cases, and complex karyotypic abnormalities were observed in 30 cases. In one case, analyzable metaphases were not obtained. The chromosomal changes were all complex and heterogeneous; no consistent presumably specific abnormality was detected. Nevertheless, two main patterns of nonrandom abnormalities were observed: 1) loss of chromosomes 4 and 22, 9p, and 3p in the most of the abnormal cases and corresponding to a hypodiploid and/or hypotetraploid modal chromosome number; and 2) gain of chromosomes 7, 5, and 20 with deletion or rearrangement of 3p as well in the hyperdiploid cases, which were a minority in our series. These findings are discussed in view of other reported cytogenetic studies of MM, asbestos exposure, and possible mechanisms of malignant transformation.