The present study, carried out in rats, is a contribution to explore physiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three groups and fed on commercial pellets: group (C) was control, group (Li1) was given 2000 mg lithium carbonate/kg of food, and group (Li2) was given 4000 mg lithium carbonate/kg of food. If we take into account the BW of the rats and the quantity of food they eat every day, we can estimate that the quantities of lithium carbonate ingested per day and kilogram of BW are, respectively, for the groups Li1 and Li2, of 212 mg (5,738 mmol Li) and 323 mg (8,742 mmol Li) for the males, and about 190 mg (5,142 mmol Li) and 289 mg (7,822 mmol Li) for the females. After 7, 14, 21 and 28 days, serum concentrations of lithium, creatinine, free triiodothyronine (FT3) and thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed together with polydipsia, polyuria, and diarrhoeLithium serum concentrations were found to increase from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Treatment was stopped at day 14 in Li2 rats because of a high mortality. The significant increase of creatinine that appeared, respectively, at day 7 and 14 in Li2 and Li1 rats shows that serum lithium concentrations ranging from 0.62 to 0.75 mM were able to induce renal insufficiency, secondarily leading to a time-dependent rise in lithium serum concentrations. A significant decrease of serum thyroxine (FT4) and triiodothyronine (FT3) levels was observed for lithium concentrations ranging from: 0.66 to 0.75 mmol l(-1) (Li2 rats) to 1.27 mmol l(-1) (Li1 rats). This effect was more pronounced for FT3, suggesting a defect of FT4/FT3 conversion. Under lithium treatment, the testosterone level decreased and spermatogenesis was stopped. By contrast, in treated female rats, estradiol level was found to be increased in a dose-dependent manner and animals were blocked in the diestrus phase at day 28. These results show that lithium can rapidly induce toxic effects in the rat at concentrations used for the treatment of bipolar disorders in human.