We studied 30 patients undergoing vitreoretinal surgery to compare the systemic absorption and cardiovascular effects of 2.5% aqueous and 2.5% viscous (21 cp) ophthalmic solutions of phenylephrine hydrochloride. No significant differences were noted in the plasma levels or changes in blood pressure between the two groups, although there was a tendency toward higher mean plasma levels and blood pressures in groups receiving 2.5% aqueous phenylephrine hydrochloride. Maximum plasma levels were achieved within the first 20 minutes following topical application of phenylephrine eye drops, irrespective of the nature of the vehicle. This finding emphasizes the importance of monitoring these patients, especially those at high risk for any adverse cardiovascular effects during the first 20 to 30 minutes following instillation of phenylephrine eye drops. The patients in our study were supine and under general anesthesia. Therefore, there was no effect by lid blinking, the lacrimal pump, or gravity, which would ordinarily increase absorption by the nasal mucosa through the nasolacrimal system. By eliminating these variable factors, such as lid blinking, the study was performed in a stable and controlled manner, but the results may not be directly applicable to an upright awake patient.