The influence of chlorthalidone on bone resorption in immobilized patients treated with mechanical ventilation was studied. Bone resorption was measured by means of urinary excretion of hydroxyproline and calcium. Blood pH was measured because of a possible effect of mechanical ventilation on calcium metabolism. Twenty-five patients were examined, 14 receiving and 11 not receiving chlorthalidone. Patients receiving chlorthalidone over a period of at least five and a maximum of 27 days showed lower hydroxyprolinuria and a higher blood pH value than the non-users. No differences were observed concerning calcium and phosphate metabolism. It is suggested that this slight alkalosis resulting from chlorthalidone may inhibit bone resorption.