Exposure to ambient air containing respirable particulate matter at concentrations below the current National Ambient Air Quality Standard has been associated with increased rates of pulmonary-related morbidity and mortality. To identify mechanisms involved in pulmonary responses to such exposure, we studied the effects of the emission source particulate air pollutant residual oil fly ash (ROFA) on prostaglandin metabolism in cultured human airway epithelial cells. Epithelial cells exposed to ROFA for 24 hr secreted substantially increased amounts of the prostaglandin H synthase (PHS) products prostaglandins E2 and F2 alpha. The ROFA-induced increase in prostaglandin synthesis was correlated with a marked increase in PHS activity. Western blots showed that ROFA exposure induced dose-dependent increases in PHS2 protein levels. Reverse transcriptase-PCR analyses demonstrated accompanying increases in PHS2 mRNA which were evident by 2 hr of continuous exposure. In contrast, expression of PHS1 was not affected by ROFA treatment of airway epithelial cells. There were no alterations in arachidonic acid release, incorporation, or availability in ROFA-exposed cells. These data show that exposure to ROFA induces PHS2 expression, leading to increased prostaglandin synthesis in cultured airway epithelial cells. These findings suggest that prostaglandins may play a role in the toxicology of air pollution particle inhalation.