The effects of the nitrovasodilator, sodium azide, on intraocular pressure (IOP) and ciliary vascular tone were compared. IOP was measured in the bovine isolated eye that was perfused via the ciliary artery. Separately, vasodilator effects were assessed after raising the vascular tone using noradrenaline (10 μM). Aqueous humor formation (AHF) rate was estimated by a fluorescein dilution method. Cyclic GMP in the ciliary processes was measured by radioimmunoassay. When compared with controls, sodium azide (10 nmole bolus dose) was found to lower IOP (2.2 ± 0.3 mm Hg; P < 0.01) via a reduction in AHF (12.19 ± 0.26 μl/min to 6.36 ± 0.53 μl/min; P < 0.001). Azide (1 μmole) also reduced ciliary vascular resistance (81.0 ± 5.5%; P < 0.01). However, the drug was 20× more potent as an ocular hypotensive than as a vasodilator (ED50 0.28 nmole on IOP, 5.55 nmole on vascular effect). Azide (10 nmole) also increased levels of ciliary cyclic GMP (127 ± 17 fmol/mg protein to 233 ± 27 fmol/mg protein; P < 0.01). The IOP-lowering effect of azide does not appear to depend on its ability to activate guanylyl cyclase (GC) in vascular smooth muscle, but rather is likely a consequence of direct activation of ciliary epithelial GC.