The oral administration of phenazopyridine hydrochloride to dogs showed that the drug accumulated selectively in lacrimal and nictitans glands and the glands of Moll, and caused a reduction of tear flow. The drug or its metabolic derivative was detectable by light microscopy as an accumulation in the cytoplasm within 48 hours after drug administration. Electron microscopy showed that the product detected was localized in secretory granules. The results suggest that phenazopyridine hydrochloride affects the synthesis of secretory granules and causes progressive destruction of affected cells.