OBJECTIVE: To compare the minimal cysticidal concentration (MCC) between Pouzolzia indica methanolic extract fraction 2 and Povidone-lodine (PVP-I) on the Acanthamoeba cyst and to illustrate the morphological changes of the cyst after being treated by light and electron microscopies. MATERIAL AND METHOD: Acanthamoeba spp were isolated from patients with Acanthamoeba keratitis and cultured on a non-nutrient agar plate (NNA) seeded with heat killed Escherichia coli (NNA-E.coli) at 37 degrees C for 7 days, adjusted to a final concentration of 10(4) cysts/ml. Several concentrations of PVP-I and fraction 2 of Pouzolzia indica methanolic extract were tested to find the minimal cysticidal concentrations (MCC) of both agents, at these concentrations there was no viable cyst which was confirmed by no excystment after further incubation for 7 days. The cysts were prepared for routine transmission and scanning electron microscopic studies. RESULTS: Structural damages of the treated cysts by MCC of PVP-I and fraction 2 of Pouzolzia indica methanolic extract showed a series of damages. Starting from shrinkage, destruction or rupture of the cyst walls and opercula, withdrawal of the cytoplasm or edema cyst by the outside solution passed through the damaged wall caused a decrease in wrinkle ridges of the ectocyst. Then the cyst was ripped and torn into small pieces CONCLUSION: MCC of PVP-I solution and the fraction 2 of Pouzolzia indica methanolic extract were 0.04% and 1:4, respectively. The structural damages were somewhat similar, such as the shrinkage, ruptured cyst wall and opercula, edema and end by breaking up of the cyst wall and degeneration of the inside cytosol. Pouzolzia indica may be modified as an effective disinfectant solution for a contact lens case if the active ingredients are more purified.