Gene-targeted mice provide a powerful approach to study the physiological and pathophysiological role of a given protein in kidney function and can give insights on the functional importance of these proteins under in vivo conditions as well as on the potential compensating mechanisms in their absence. Full utilisation of these animal models requires adaptation of the respective methods to the size of the mouse. This applies especially to in vivo studies in mice which have to deal with rather small structures and volumes, e.g. vessels for cannulation, plasma volumes or urinary flow rates. Here some aspects which can help to study kidney function in the mouse in vivo are outlined. The applicability of these in vivo methods are stressed by reviewing their very recent application in mice being deficient for either ROMK or SGK1.