The effect of mucoadhesive polymeric vehicles on the mydriatic efficacy, and on the systemic and ocular absorption of cyclopentolate from eyedrops was studied in albino rabbits. Combining cyclopentolate base to polygalacturonic (CY-PGA) or hyaluronic (CY-HA) acid resulted in an increased mydriatic effect when compared with cyclopentolate hydrochloride (CY-HCl). During the first half an hour, the systemic absorption of cyclopentolate was lower after CY-PGA than after CY-HCl. The ocular penetration of cyclopentolate, based on drug concentrations in aqueous humor 30 minutes after the eyedrop instillation, was increased 3 fold when the polygalacturonate complex was used. CY-PGA, as well as other polymeric salts, might offer a possibility to increase the therapeutic index of cyclopentolate.