The present study examines whether changes in the alveolar pressure (PA) affect the single breath diffusing capacity for carbon monoxide (DLCO) more strongly at mid-lung volume than at total lung capacity (TLC) in normal subjects. DLCO was measured at 60%, 80% and 100% of TLC, while PA was kept at +30, 0, or -30 cm H2O by the subject's effort during the measurement of DLCO at each lung volume. The capillary blood volume (Vc) and the membrane diffusing capacity (Dm) were also determined. DLCO at zero PA was found to be higher at 100% TLC than at lower lung volumes. At PA = +30 cm H2O, DLCO at 100%, 80%, and 60% TLC decreased by 8%, 13%, and 13%, respectively, and the decreases in Vc were 2%, 10%, and 21%, respectively. However, negative PA did not cause any significant changes in DLCO or Vc at any lung volume. Also, Dm did not change at any PA. We conclude that DLCO is more affected by a positive PA at mid-lung volume than at a high lung volume, probably due to a greater decrease in Vc.