The CT features of benign and malignant pleural diseases have been described. However, the accuracy of these features in the differential diagnosis of diffuse pleural disease has not been assessed before. Without knowledge of clinical or pathologic data, we reviewed the CT findings in 74 consecutive patients with proved diffuse pleural disease (39 malignant and 35 benign). The patients included 53 men and 21 women 23-78 years old. Features that were helpful in distinguishing malignant from benign pleural disease were (1) circumferential pleural thickening, (2) nodular pleural thickening, (3) parietal pleural thickening greater than 1 cm, and (4) mediastinal pleural involvement. The specificities of these findings were 100%, 94%, 94%, and 88%, respectively. The sensitivities were 41%, 51%, 36%, and 56%, respectively. Twenty-eight of 39 malignant cases (sensitivity, 72%; specificity, 83%) were identified correctly by the presence of one or more of these criteria. Malignant mesothelioma (n = 11) could not be reliably differentiated from pleural metastases (n = 24). We conclude that CT is helpful in the differential diagnosis of diffuse pleural disease, particularly in differentiation of malignant from benign conditions.