Micropuncture studies were performed in rats infused with LiCl to induce stable plasma lithium concentrations of 2--3 mEq/l, or with an equivalent amount of NaCl. In free flow experiments LiCl reduced proximal tubule fractional reabsorption of sodium and potassium. Reduced reabsorption of bicarbonate, as reflected by a decrease in TF/PCl, was also observed. Proximal fractional reabsorption of chloride, however, was not affected. The TF/PIn at the end proximal tubule was 2.6 +/- 0.2 (mean +/- SEM) in controls and 2.1 +/- 0.1 in the experimental animals (P less than 0.025). In the distal portions of the nephron lithium treatment caused a fall in fractional reabsorption of water and sodium, while potassium secretion was stimulated in the distal tubule. Previous studies have indicated that lithium influences antidiuretic hormone stimulated water transport in the collecting duct. These experiments demonstrate that lithium also affects the transport of water and electrolytes in multiple nephron segments, including the proximal and distal convolution.