Can urolithiasis start as an intratubular event? Under severe hyperoxaluric conditions in animal models at least crystal formation can. Recently models have been presented that assess the chances of crystal formation under more normal conditions. These models describe changes in fluid composition as this passes through the nephron, these conditions being simulated in in vitro experiments. It appears that under naturally occurring intratubular conditions calcium-salt crystallization takes place within the time tubular fluid normally spends in the nephron. Precipitation starts with a calcium-phosphate phase under conditions found in the thin lambs. This crystalline phase then (partly) dissolves when collecting duct conditions are used, thereby inducing formation of calcium oxalates. Under these conditions the latter increase in size by way of crystal growth and agglomeration. Large particle formation and cell adhesion can eventually result in particle retention and subsequent stone formation. Viewing urolithiasis as originally an intratubular event has consequences for in vitro experiments and treatments, which are discussed in this paper.