Effects of PGE 1, PGE 2 and PGE 2α on the electrical parameters and unidirectional chloride flux across the isolated toad ciliary epithelium and cyclic-AMP content of the tissue have been investigated. Addition of prostaglandins to the bathing solutions caused a sustained decrease in the short-circuit current without appreciable change in the electrical resistance. The effects of prostaglandin added to the epithelial side were much faster and stronger than when added to the stromal side. The order of potency of the inhibitory action was PGE 1>PGE 2≧PGF 2α, The minimum effect was observed at doses greater than 10 −8 g/ml for PGE 1 and 10 −6 g/ml for PGE 2 and PGF 2α. Addition of Dbc-AMP to the epithelial side caused a similar change in the short-circuit current to those elicited by prostaglandins. Tissue content of cyclic-AMP increased immediately and significantly after the addition of PGE 1. Unidirectional chloride flux from the stromal to epithelial side was decreased by PGE 1, while the flux in the opposite direction increased very slightly. Consequently, the net chloride flux toward the epithelial side decreased considerably. These results suggest that prostaglandins exert their inhibitory action on the active chloride transport across the toad ciliary epithelium through the binding with a receptor site at the aqueous-facing membrane, stimulation of the adenylate cyclase activity and elevation of the cellular level of cyclic-AMP. Passive permeability of the epithelium to NaCl appeared to be unaffected by prostaglandins.