Rats and guinea-pigs were given LiCl acutely (2 mmol/kg IP or intragastrically) or chronically (daily doses 0.6-4 mmol/kg) and plasma, erythrocytes, kidney, liver and brain were analysed for Li+. Generally, after acute LiCl, tissue Li+ levels followed changes in plasma Li+ levels. However, brain Li+ concentrations changed more slowly and in the rat, but not in the guinea-pig, paralleled erythrocyte Li+ concentrations. Li+ was absorbed more slowly from the gastrointestinal tract of the rat. After chronic LiCl, the erythrocyte:plasma Li+ ratio was about 0.1 in the guinea-pig and about 2 in the rat. Relative Li+ tissue concentrations were as follows: guinea-pig, plasma greater than kidney greater than liver greater than brain greater than erythrocyte;rat much greater than erythrocyte = brain greater than liver = plasma. A Na+-dependent Li+ efflux was demonstrated in the erythrocytes of the guinea-pig and human, but not the rat. This process was inhibited by phloretin (0.2 mM), but not frusemide (2.0 mM). The marked differences in the activity of the erythrocyte Na+-dependent Li+ countertransport process in the guinea-pig and rat could extend to other tissues and explain the observed interspecies differences in tissue Li+ distribution.