OBJECTIVE To determine the effect of orally administered melatonin on the intraocular pressure (IOP) of ophthalmologically normal dogs. METHODS 20 ophthalmologically normal dogs (40 eyes). METHODS In a randomized crossover study, each dog received a 7-day regimen of melatonin (0.1 to 0.2 mg/kg, PO, q 12 h) and a placebo (150 mg of lactose powder in a capsule, PO, q 12 h), with a 7-day washout period between treatment regimens. Rebound tonometry was used to measure the IOP in both eyes of each dog 5 times at 2-hour intervals on days 0 (before administration of the first dose), 2, 4, and 7 (after administration of the last dose) of each treatment period. Repeated-measures ANOVA was used to evaluate the effects of treatment, day, and IOP measurement time within day on IOP. RESULTS Intraocular pressure was not significantly associated with treatment but was associated with day and the interaction between day and IOP measurement time within day. The mean ± SD IOP was 14.26 ± 2.95 and 14.34 ± 2.69 mm Hg for the melatonin and placebo regimens, respectively. Within each treatment period, the mean IOP tended to decrease from day 0 to 7 as well as within each day, which was attributed to the dogs becoming acclimated to the study protocol and natural diurnal variations in IOP. CONCLUSIONS Results indicated that oral administration of melatonin (0.1 to 0.2 mg/kg, q 12 h for 7 d) did not significantly affect the IOP of ophthalmologically normal dogs.