Guanosine derivative 1 forms hydrogen-bond-directed giant vesicles. On a silicon substrate, the vesicles retain their shape and internal water phase even after removal of external water under vacuum. Dry manipulation of the micrometer-sized vesicles was carried out via AFM-tip-induced partition and fusion of the vesicles. For larger vesicles (5-10 mu m), external solutions were successfully injected through a microcapillary inserted into the vesicle in air.