To determine the significance of an isolated reduction in residual volume (RV), the medical records and chest radiographs of 69 patients who had a RV less than or equal to 65% of predicted and normal VC, DLCO, and expiratory flow rates were reviewed. Sixty-three of 69 patients (92%) had clinical conditions that could account for their decreased RV. Definite disease was considered to be present in the 39 patients with radiographically apparent parenchymal (n = 18) or chest wall (n = 21) abnormalities, whereas 24 others with clinical diagnoses such as congestive heart failure or toxic inhalation were considered to have probable disease. All patients who had a RV below 50% of predicted had either definite or probable disease. Follow-up testing of 19 patients 31 +/- 21 months after their initial reduction in RV was first documented indicated that the RV accurately reflected the patient's current clinical status in that it increased by 17 +/- 16% of predicted in those who were clinically improved and decreased by 27 +/- 7% in those who were clinically worse. In patients who were clinically stable, the isolated reduction in RV was a persistent finding. We conclude that an isolated reduction in RV is a clinically significant finding indicative of pulmonary or chest wall disease. Interval changes in RV reflect alterations in disease activity.