Single crystals of a neutral, microporous, laminated metal–organic framework (MOF) [Fe(pydc)(4,4′-bipy)]·H₂O (1·H₂O) (H₂pydc = 2,5-dicarboxypyridine, 4,4′-bipy = 4,4′-bipyridine) were generated by hydrothermal synthesis, and its crystal structure was determined. 1·H₂O retains the framework robustness to ca. 370 °C and is insoluble in common organic solvents. By soaking in MeOH and EtOH solutions, 1·H₂O was transformed directly from the parent single crystals into single crystals of 1·MeOH or 1·EtOH, respectively. Meanwhile, 1·H₂O shrank to the guest-free framework 1_h or 1_v, respectively, under appropriate heating (up to 160 °C in N₂) or vacuum treatment (10 mmHg) at room temperature. Compared to that of 1·H₂O, the unit-cell volume of 1·EtOH slightly increases by 2.9%, whereas those of 1_h or 1_v are reduced by 8.2 and 6.6%, respectively. The anhydrous 1_v was found to be highly chemically reactive, taking up ethanol vapor to furnish the solvated crystal structure of an ‘expanded’ framework 1·EtOH. In a mixture of ethanol–DMF or ethanol–benzene, a selective exchange process was observed, with only ethanol molecules exchanged into the structure due to the limited free size of the channels in the framework of 1. All the transformed crystals have also been characterized by X-ray single-crystal diffraction to understand the crystal-to-crystal transformation, which have different free volumes (6.5–20.4%).