Nucleolar organiser regions represent nucleolar activity in both normal and malignant cells. More numerous nucleolar organiser regions have been found in cells from many forms of malignancy than in normal cells. An argyrophilic method of staining these regions (the AgNOR technique) has been applied to specimens of pleura obtained by biopsy or at necropsy in an attempt to differentiate between normal, "reactive," and malignant pleural disease. The number of nucleolar organiser regions in samples taken from 10 patients with normal pleura (mean 1.04 (95% confidence interval 0.96-1.12] was less than the number seen in samples from 10 patients with "reactive" (inflammatory) pleural disease (1.75 (1.34-2.16); p less than 0.001). This is the first demonstration of increased numbers of nucleolar organiser regions in an inflammatory condition. In specimens from 25 patients with mesothelioma the corresponding numbers of nucleolar organiser regions were: tubulopapillary (n = 10) 5.43 (4.42-6.44); undifferentiated (n = 5) 5.00 (3.29-6.71); sarcomatous (n = 5) 7.52 (3.96-11.08); and mixed histological types (n = 5) 4.94 (3.2-6.68). All these values differ significantly from those for both normal and "reactive" tissue (p less than 0.001). It is concluded that the AgNOR technique separates "reactive" pleural disease from mesothelioma with a high degree of confidence and is an important advance in the diagnosis of malignant mesothelioma.