The role of nitric oxide in allergic conjunctivitis was studied in a guinea pig model. The eyes of sensitized guinea pigs were challenged with ovalbumin (20 micrograms per eye) or histamine (20 micrograms per eye). Synthesis of nitric oxide (NO) was inhibited using L-NAME (200 micrograms per eye) or aminoguanidine (200 micrograms per eye). The formation of conjunctival edema was graded and levels of nitrite, a breakdown product of nitric oxide were measured in lavage fluid. Conjunctival vasopermeability was determined by measuring the albumin concentration in the fluid on the surface of the eye (lavage fluid). Animals were treated with sodium nitroprusside (SNP) or phenylephrine after which histamine induced conjunctival vasopermeability changes were measured. Drugs were administered topically with the other eye serving as a control. Both ovalbumin and histamine produced a marked inflammatory response including hyperaemia and edema. At the top of the inflammatory response occurring 30 min after challenge, increased levels of nitrite, a breakdown product of NO, were measured in lavage fluid. Prophylactic treatment with L-NAME or aminoguanidine resulted in a significant inhibition of the NO synthesis. Both L-NAME and aminoguanidine decreased conjunctival vascular permeability and edema formation significantly. Administration of SNP resulted in a marked dilatation of conjunctival blood vessels and produced a dose-dependent increase of vascular permeability. Addition of SNP to histamine significantly enhanced conjunctival edema and potentiated vascular permeability. These results indicate that NO is produced in the acute phase of allergic conjunctivitis and mediates vasodilatation after topical provocation with ovalbumin or histamine in sensitized guinea pigs. The resulting increase of the conjunctival blood flow subsequently increases the vascular permeability and enhances conjunctival edema formation. Inhibition of NO synthesis leads to a reduction of conjunctival hyperaemia and subsequently reduces the formation of edema.