The clearance rate of an inhaled aerosol of a lipophilic complex, 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO), was compared with that of a hydrophilic complex, 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA), in nine normal subjects and in eight patients with idiopathic pulmonary fibrosis (IPF). Data were acquired as follows. The subjects were placed supine with their back against the scintillation camera and breathed aerosol for 2 min; pulmonary radioactivity was then monitored for 30 min. A time-activity curve (TAC) was generated from the region of interest (ROI) over the periphery of each lung field and a computer program was then used to calculate percentage clearance per minute (k) in each lung. The mean (+/- S.E.M.) rate of clearance of 99Tcm-DTPA (k = 1.31 +/- 0.13% min-1) was not significantly different from that of 99Tcm-HMPAO (k = 1.32 +/- 0.27% min-1, P > 0.025) in the normal subjects. However, 99Tcm-DTPA clearance was 1.91 +/- 0.27% min-1 and 99Tcm-HMPAO clearance 0.78 +/- 0.17% min-1 in eight patients with IPF (P < 0.001, 99Tcm-DTPA vs 99Tcm-HMPAO). By regression analysis using a multiplicative model, both values correlated fairly [r = -0.71, y = exp (0.08-0.85 ln chi); P < 0.005], with a change in clearance rate in the opposite direction in all eight patients. The results of our study demonstrate that the pulmonary clearance of 99Tcm-HMPAO is different from that of 99Tcm-DTPA in IPF.