Histological lesions in man, presumably indicating kidney damage, may occur during therapy with lithium carbonate. We studied the cellular effects of lithium carbonate applied in vitro to slices of kidney from adult female Sprague-Dawley rats. Alternate slices were immersed in saline solution containing 1.1 mEq/L of lithium carbonate; the other slices were immersed in ordinary saline solution as controls. Compared with control specimens, a two-hour incubation in lithium carbonate solution showed (1) with toluidine blue 0, in the cells of the collecting ducts a fibrous metachromatic network that was interpreted as indicating microtubule bundles; and (2) with Brookes' stain in the proximal convolutions, increased acidophilia of the hyaline droplets and of the nucleus that implied interaction of lithium carbonate with the protein transport and degradation mechanism located in these cells. The results can be interpreted as being due to polymerizations or to conformational changes of protein components caused by lithium. These changes are consistent with altered functions of the kidney observed in manic-depressive patients receiving treatment with lithium carbonate, which lead to polyuria (collecting ducts) and may lead to nephrotoxicity (proximal convolutions).