Acute exposure of humans to low levels of ozone are known to cause decreases in FVC and increases in SRaw. These alterations in lung function do not, however, elucidate the potential for acute small airway responses. In this study we employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy nonsmoking male volunteers were exposed to 0.4 ppm ozone for 1 h while exercising at 20 L/min/m2 body surface area. Before and immediately after exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and piethysmography (Raw and SRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300-ml bolus of a 0.5-mu-m triphenyl phosphate aerosol injected into a 2-L tidal volume. The bolus was injected into the tidal breath at three different depths: at Depth A the bolus was injected after 1.6 L of clean air were inhaled from FRC, at Depth B after 1.2 L, and at Depth C after 1.2 L but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW). Secondary measures were the ratio (expressed as percent) of peak exhaled aerosol concentration to peak inhaled concentration (PR), shift in the median bolus volume between inspiration and expiration (VS), and percent of total aerosol recovered (RC). Changes in pulmonary function after ozone exposure were consistent with previous findings. When corrected for exercise, FVC, FEV1, and FEF25-75 all significantly declined (p < 0.001, p < 0.002, and p < 0.03, respectively), with nonsignificant increases in Raw and SRaw. HW significantly increased after ozone exposure relative to air exposure at all depths (17 ml p < 0.05 at Depth A, 56 ml p < 0.001 at Depth B, and 53 ml p < 0.005 at Depth C). Of the other dispersion measures, PR and PC decreased significantly only at Depth B (-4.9%, p < 0.001 and -3.9% p < 0.05, respectively). HW was only weakly correlated with spirometric measures, accounting for less than 25% of the variance. Half-width was not correlated with Raw or SRaw. We conclude that the changes in aerosol dispersion seen with ozone exposure are related to changes in turbulent mixing and/or regional time constants in the small airways, thus suggesting a possible ozone effect in that region of the lung.