Abstract: Methods of treating fluid retention disorders with the B isomers of guanylin family peptides are described herein. UgnB, when compared to the A isomer (UgnA), exhibits a conventional sigmoidal dose-response relationship in its natriuetic activity. Further, unlike UgnA, UgnB only weakly activates the GC-C receptor. Compositions comprising purified, or mixtures containing B isomers of guanylin family peptides are described herein are therefore useful for the treatment of fluid retention disorders.