Melatonin injected into the vortex vein of a rabbit eye produced an increase in intraocular pressure (IOP) which lasted for up to 5 h. Injection of haloperidol caused a decrease in IOP; this effect was totally reversed by melatonin. It is probable that these effects are caused by physiological antagonisms. Injection of the mu opiate agonist (D-ala2-n-methyl-ph2-gly5-ol) enkephalin caused a decrease in the IOP of artificially ventilated rabbits and a decrease in melatonin levels in iris, iris root-ciliary body, and retina of the rabbit eye. Melatonin levels did not decrease after anesthesia with rompunketamine. It is probable that the decrease in melatonin levels is specific to certain classes of opioids, and endogenous opioids may play a role in the regulation of ocular melatonin levels and hence IOP.