In the present study the effects of P-adrenergic antagonist and a-adrenergic agonist drugs on rabbit corneas were evaluated in vivo by using transmission electron microscopy. Twenty-four New Zealand albino rabbits were divided into six groups according to the drug applied. The rabbits to which only balanced salt solution (BSS) or BSS and benzalkonium chloride (BAC) were applied were taken as the control groups. The other four groups consisted of the rabbits to which Timoptic 0.5%, Betagan 0.5%, Betoptic 0.5% and lopidine 1% were applied, respectively. All of drugs were instilled topically twice dal ly for 6 weeks. In the BSS group, a II layers of the cornea were ultrastructurally normal. In the BSS and BAC group slight epithelial and endothelial changes were found. However, in the other groups, loss of microvilli, increase in glycogen particles, nuclear indentation, widening of the intercellular spaces and cytoplasmic vacuolization in epithelium were observed. No significant abnormality was found in the basal lamina, stroma and Descemet's membrane. Slight ultrastructural changes were noted in the endothelium such as vacuolization due to dilatation of the endoplasmic reticulum cisternae and focal cytoplasmic lytic areas. The results of this study indicate that various ultrastructural changes occur in groups treated with antiglaucomatous drug and that topical treatment with timolol and apraclonidine for 6 weeks is more toxic to the rabbit cornea than levobunolol and betaxolol.