The pyrazinyl-1,2,4-oxadiazoles 4a and 4b were synthesized by two different approaches. The corresponding N-methyloxadiazolium salts 13a and 13b were also prepared. These compounds were evaluated for their diuretic and saluretic activity in rats and dogs. All compounds exhibited electrolyte excretion profiles similar to amiloride 1. The facile conversion of 4a to 1 was demonstrated chemically and in vivo in both rats and dogs.