Background: Even after a complete work-up including thoracoscopic biopsies, a significant number of patients with pleural exudates are diagnosed with ‘non-specific pleuritis’, and no specific diagnosis can be made. The natural evolution of these patients is poorly understood. Objectives: To study the natural evolution of patients with non-specific pleuritis diagnosed after thoracoscopy and to evaluate whether the histological diagnosis of non-specific pleuritis corresponds with the clinical diagnosis of ‘idiopathic pleuritis’. Methods: We retrospectively studied the evolution of 75 patients between 1992 and 2002 (49 men and 26 women), mean (± SD) age 63.4 (± 13.3) years, who underwent diagnostic thoracoscopy because of an unexplained exudative pleural effusion, and in whom the histological diagnosis of non-specific pleuritis was made. Follow-up data were obtained through medical files and/or telephone contacts with general practitioners. Results: Of these 75 patients, 8.3% eventually developed a malignancy during the follow-up period. In the remaining patients (91.7%), the clinical evolution followed a benign course. Ultimately, a probable cause was established on clinical grounds in 40 patients. True idiopathic pleuritis was finally observed in 25% of patients with the histological diagnosis of non-specific pleuritis. Recurrence of the effusion occurred in 10 out of 60 (16.7%) patients, after a mean period of 26.2 months. Conclusions: The majority of non-specific pleuritis patients (91.7%) followed a benign course, with a spontaneous resolution of the effusion in 81.8% of cases. In the majority of patients, a probable cause of the pleuritis was identified. True ‘idiopathic benign pleuritis’ hence occurs in only a minority (25%) of patients.