Both Δ9-tetrahydrocannabinol ( Δ9-THC) and cannabigerol, two naturally occurring marihuana cannabinoids, produced only a modest fall in intraocular pressure after acute topical application to the eyes of cats. After chronic administration unilaterally to the cornea via Alzet® osmotic minipumps and connecting extraocular cannulas, however, a considerable fall in ocular tension amounting to 4 to 7 mm Hg occurred. After systemic administration of Δ9-THC to rats, polyspike discharges appeared in the cortical electroencephalogram initially during wakefulness and behavioral depression. These polyspikes subsequently became evident within rapid eye movement sleep episodes. Cannabigerol was devoid of this effect. After removal of either sympathetic or parasympathetic input to the eyes of cats, the intraocular pressure lowering effect of Δ9-THC was not changed. Neither Δ9-THC nor cannabigerol altered the rate of formation of aqueous humor. On the other hand, both cannabinoids produced a two-to three-fold increase in aqueous outflow facility. These results suggest that cannabigerol and related cannabinoids may have therapeutic potential for the treatment of glaucoma.