PURPOSE. Ibopamine is a prodrug of epinine (deoxyepinephrine) that exhibits activity at dopaminergic and adrenergic receptors. Topical ocular application has been shown to cause mydriasis without cycloplegia and to increase the rate of aqueous humor flow in normotensive human eyes. Mydriasis can interfere with the measurement of aqueous flow. In this study ibopamine's effect on aqueous humor production was measured while making allowance for the potential artifact caused by its mydriatic effect. METHODS. The effects of topical ibopamine on pupillary diameter, aqueous humor flow measured by fluorophotometry, and intraocular pressure were studied in 24 healthy, blue-eyed humans. Ibopamine was administered with and without the α-adrenergic antagonist dapiprazole, and its effects were compared with those of tropicamide, with and without dapiprazole in a double-masked, randomized, crossover design. RESULTS. Ibopamine dilated the pupil from a diameter of 3.7 ± 0.64 (mean ± SD, n = 24) to 7.7 ± 0.70 mm. Ibopamine, during its peak mydriasis, was associated with a very large increase in the rate of clearance of topically applied fluorescein from the cornea and anterior chamber, an effect that was not associated with tropicamide during its peak mydriasis. The mydriatic effect of ibopamine was completely blocked by dapiprazole, and the increase in fluorescein clearance was partially blocked. When mydriasis was blocked, ibopamine increased fluorescein clearance by 13% (P < 0.0001), which was interpreted as an increased rate of aqueous humor production. Compared with placebo and with the tropicamide control, ibopamine decreased intraocular pressure, despite its stimulation of aqueous humor flow. CONCLUSIONS. Ibopamine is in a specific class of drug, along with pilocarpine, epinephrine, and bimatoprost that in humans increases the rate of aqueous humor flow as measured by fluorophotometry. This effect is partly responsible for its ability to increase intraocular pressure in persons suspected to have abnormally low aqueous humor outflow facility. The transient apparent doubling of aqueous humor flow, measured by fluorescein clearance after administration of ibopamine is an artifact of increased fluorescein clearance through the dilated pupil while accommodation is active.