Intrapleural instillation of tetracycline (TCN) has been shown to be effective in preventing the recurrence of malignant pleural effusions. Although the precise mechanism of action is unknown, it has been postulated that the pH of the TCN solution may be an important factor. Thirty patients with malignant pleural effusions were randomized in a double-blind trial to receive intrapleural administration of either 500 mg of tetracycline in solution (pH = 2.8) or a solution of similar pH and appearance. All patients had chest tube drainage of their effusion. There were 24/30 patients evaluable. There were 9/13 patients in the TCN group and 1/9 patients in the control group who had no reaccumulation of fluid (P less than 0.05). These results would suggest that the efficacy of TCN as a sclerosing agent is not related to its acidic pH and that intrapleural TCN is more effective than chest tube drainage alone for control of malignant effusions.