The levels of leukotriene C₄ (LTC₄), leukotriene B₄ (LTB₄), prostaglandin E₂ (PGE₂), and histamine were measured in nasal lavage fluids obtained from aspirin-sensitive, desensitized aspirin-sensitive, and aspirin-insensitive asthmatics and normal volunteers before and after ingestion of aspirin. Increased levels of LTC₄ and histamine were associated with significant decreases in the FEV₁ for 3 of 4 aspirin-sensitive asthmatics who had both naso-ocular and bronchospastic reactions to aspirin. In contrast, no increase in LTC₄ or histamine release was detected in aspirin-sensitive asthmatics who had only bronchospastic reactions to aspirin. No significant decreases in PGE₂ levels or increases in LTB₄ levels were detected during these reactions to relatively low doses of aspirin regardless of the clinical symptoms, nor was any increase in mediator release apparent in lavage fluids from normal donors, aspirin-insensitive asthmatics, and desensitized aspirin-sensitive subjects before or after various doses of aspirin. Levels of PGE₂ decreased in nasal secretions from normal volunteers, aspirin-insensitive asthmatics, and desensitized aspirin-sensitive subjects after ingestion of 650 mg of aspirin. These decreases were not associated with increased LTC₄ or LTB₄ or with histamine release, decreased FEV₁, or naso-ocular symptoms. In addition, reductions of PGE₂ release were similar for normal and desensitized aspirin-sensitive volunteers (63 ± 11 versus 61 ± 10%, respectively). The data demonstrate that LTC₄ and histamine are released into nasal secretions of aspirin-sensitive asthmatics with naso-ocular and bronchospastic reactions after ingestion of low doses of aspirin without a decrease in the levels of PGE₂ and suggest that LTC₄ and histamine contribute to the naso-ocular and bronchospastic symptoms characteristic of reactions to aspirin.