Relationships of lung mechanics and diffusion to lung volume were examined in 38 patients with interstitial lung disease to determine whether patterns of reduction relate to severity of disease, distinguish histologic characteristics or predict prognosis for reversibility. Normal volume-related values for both mechanics and diffusion were seen throughout the range of severity of disease. The ratio of mechanics to lung volume did not correlate with the ratio of diffusion to lung volume in the same patient. Volume relationships of mechanics and diffusion failed to distinguish pathologic predominance of fibrosis or inflammation/granulomas. These ratios failed to predict reversibility in patients who had repeated tests. These results suggest that in patients with interstitial lung disease the significance of "volume-adjustment" of mechanics and diffusion should be viewed with caution; these parameters do not appear to contribute to the assessment of pathophysiology or correlate with clinical spectrum of interstitial lung diseases.