Platelet-activating factor (PAF) is a short-acting, lipid-soluble autocoid, inhalation of which causes an immediate pulmonary vascular sequestration of granulocytes and a peripheral neutropenia. We investigated the effect of PAF inhalation on the pulmonary clearance rate of inhaled 99mTc-DTPA in order to test the hypothesis that the pulmonary sequestration of granulocytes results in acute lung injury. In nine normal nonsmoking adults, the rate of clearance of DTPA, corrected for background activity, was 1.5 (SD 0.7) %/min over the first 10 min after inhalation. Inhalation of 4.8 micrograms PAF abruptly increased the clearance rate to a mean value of 2.3 (1.4) %/min (p < 0.05). No increase in clearance was observed in four nonsmoking subjects who inhaled vehicle only. The mean overall increase after PAF was 87% of the baseline clearance, significantly different (p < 0.05) from the corresponding change in the control group, which was -17%. After PAF, the clearance rate returned to baseline values within 10 min in all subjects. In all subjects who inhaled PAF, but in none who inhaled vehicle, there was an immediate neutropenia of 51 (SD 25) % of the baseline value (p < 0.01). This neutropenia persisted longer than the corresponding accelerated DTPA clearance and was still 74 (36) % of the baseline value at 10 min. Furthermore, there was no correlation between the increase in DTPA clearance induced by PAF inhalation and the decrease in peripheral blood granulocyte count. We conclude that PAF inhalation results in an increase in pulmonary DTPA clearance, probably not mediated by pulmonary vascular granulocyte sequestration.