STUDY OBJECTIVE To determine whether the measurement of pleural fluid pH in malignant effusions has diagnostic use, predicts survival, and has therapeutic implications. DESIGN A prospective comparison of cytologic examinations and pleural biopsy results, survival, and response to chemical pleurodesis with tetracycline in patients with normal-pH (7.30 or greater) and low-pH (less than 7.30) malignant pleural effusions. SETTING Academic medical center, university referral hospital, city hospital, and Veterans Administration hospital. PATIENTS Sixty patients with malignant pleural effusions, proven at either initial thoracentesis by cytologic examination or within 4 months of initial thoracentesis by repeat thoracentesis, thoracotomy, or autopsy, were followed until death. INTERVENTION Twenty-one patients, 12 with normal pleural fluid pH and 9 with low pleural fluid pH, were treated with tube thoracostomy and intrapleural tetracycline for symptomatic, recurrent pleural effusions. MAIN RESULTS The 20 patients with low-pH malignant effusions had a significantly greater positivity on initial pleural fluid cytologic evaluation, a shorter mean survival, and a poorer response to tetracycline pleurodesis compared with 40 patients with normal-pH malignant effusions. CONCLUSIONS Determination of pleural fluid pH in malignant effusions provides a rational approach to further diagnostic testing, prognostic information, and a rationale for palliative treatment.