The crystal structures of the commercially available form of erythromycin A dihydrate and clarithromycin anhydrate, in addition to the structure of erythromycin B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of erythromycin A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of erythromycin A is stored under conditions of low relative humidity. Although erythromycin A dihydrate retains its crystallographic order at low humidity, as indicated by its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced by the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.