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1. Reduction in osmolality of the Ringer solution bathing the morphological inside of frog skin (by lowering the NaCl concentration) caused a significant increase in sodium transport as measured by the short-circuit current. Pretreatment of the skin with acetylsalicylic acid (2·5 x 10^-4 M) abolished the short-circuit current and open-circuit potential responses to osmolal change.

2. The output of prostaglandin-like material from isolated frog skin was increased by incubating the skin in hypotonic Ringer solution.

3. The cyclic AMP levels of isolated frog skin were also increased by a reduction in the osmolality of the Ringer fluid bathing the skin.

4. Prostaglandin-like material was released both by the separated epithelial and dermal layers of frog skin and the output from both layers, on a unit wet weight basis, did not differ.

5. The output of prostaglandin-like material from the separated layers of the skin was substantially greater than from whole skin. Indomethacin (6 x 10^-6 M) reduced the output of this material by more than 90% from both layers.

6. The release of prostaglandin-like material from the separated layers of the skin was not altered by a reduction in osmolality of the bathing medium.

7. It is concluded that a reduction in the osmolality of the solution bathing frog skin stimulates prostaglandin production and that the increased level of prostaglandins stimulates transepithelial sodium transport by stimulating cyclic AMP accumulation. It is also concluded that the response to osmolal change can only occur in intact skin since separation of the epithelial and dermal layers abolished the increase in the release of prostaglandin-like material to osmolal change. The site of the increased prostaglandin production and the exact nature of the stimulus remain to be determined.