ME1 is a monoclonal antibody which is generated by the use of a mesothelioma cell line (SPCIII). The antibody has a preferential reaction to antigens on mesothelial and mesothelioma cells. In a prospective study we determined the reactivity in frozen sections from malignant mesotheliomas (two cases, positive controls), lung tumours (115 cases) and other malignant tumours (23 cases). The two malignant mesotheliomas were immunoreactive in most of the tumour cells. The reaction was strong, often with a diffuse staining of the cytoplasm and in some tumour cells there was heavy staining of the cell membrane. Five adenocarcinomas of the lung (9%), one large cell carcinoma (10%) and 18 squamous cell carcinomas of the lung (41%) were positive (defined as tumours containing more than 10% positive tumour cells with a strong reaction). The same was true for seven out of 23 (30%) extrapulmonary malignancies. The overall nosologic specificity of ME1 was 76%. Twenty out of the 26 ME1-positive lung tumours and six out of seven ME1-positive extrapulmonary malignancies were also positive for one or more markers, which is considered characteristic of carcinomas. The six negative lung tumours were squamous cells carcinomas and the negative extrapulmonary tumour was a meningeoma; all of them with a morphology different to malignant mesothelioma. In conclusion, when frozen sections are available, ME1 might be useful in the differential diagnosis of malignant tumours. However, a positive reaction is not specific for malignant mesothelioma.