To investigate the potential effects of inhaled platelet-activating-factor (PAF) (12 micrograms) to perturb pulmonary gas exchange in bronchial asthma, six patients (mean +/- SE, 23 +/- 2 yr) with intermittent asthma (FEV1, 90% predicted) were studied before and 5, 15, and 45 min after challenge. Circulating white blood cells, respiratory system resistance (Rrs), systemic and pulmonary hemodynamics, and respiratory and inert pulmonary gas exchange were measured. Five minutes after PAF leukocytes fell, Rrs increased (by 27%). PaO2 decreased (by 15 mm Hg), and AaPO2 increased (twofold) (p < 0.05 each). Ventilation-perfusion (Va/Q) distributions worsened in a pattern similar to that commonly observed in patients with moderate to severe asthma. Dispersions of pulmonary blood flow (log SD Q) and of alveolar ventilation (log SD V), and an overall index of Va/Q heterogeneity (DISP R-E*) increased significantly (123% for DISP R-E*; p < 0.05, each). Gas exchange indices and Rrs were still minimally abnormal at 15 min but returned towards baseline at 45 min. Ventilatory and hemodynamic variables remained unaltered throughout the study. These results suggest that endogenous PAF may be implicated in the arterial blood gas abnormalities shown during exacerbations of bronchial asthma.