This study was carried out to investigate the characteristics of lithium concentration difference between maternal and fetal plasma and the effect of previous lithium loading on rapid transplacental transport of large amounts of lithium. Pregnant rabbits at 20 ~ 22 days of gestation were divided into two groups: chronic Li⁺ injection group and chronic plus acute Li⁺ injection group. Small amounts of LiCl (1 mmol/kg per day) were given intraperitoneally to all rabbits of both group, for 5 days before sacrifice. The rabbits of chronic plus acute injection group, received additional intravenous injections of large amounts of LiCl (2 mmol/kg) one hour before sacrifice. Maternal arterial blood, placental sinus blood, fetal blood and amniotic fluid were drawn and analyzed for the plasma concentrations of Li⁺, Na⁺ and K⁺ and for osmolartiy. Followings are the results obtained. 1) There was no difference in the Li⁺ concentration between maternal plasma and placental sinus plasma in chronic lithium group, although the Li⁺ concentration of placental sinus plasma was slightly lower than that of maternal arterial plasma in the chronic plus acute lithium group. 2) The Li⁺ concentration of fetal plasma was much lower than that of placental sinus plasma in both groups, the ratio being 0.76±0.250 (mean±95% confidence interval) for the chronic Li⁺ group and 0.78±0.366 for the chronic plus acute Li⁺ group. 3) The ratio of Li⁺ concentration of fetal plasma to maternal arterial plasma was 0.71±0.196 in the chronic group and 0.59±0.261 in the chronic plus acute group. 4) Li⁺ concentration of amniotic fluid was much higher than that of fetal plasma in the chronic Li⁺ group but not significantly different in the chronic plus acute Li⁺ group. 5) An acute loading of Li⁺ did not produce any detectable changes in Na⁺ and K⁺ concentrations and osmolarity of the maternal plasma. The above results may suggest that: (a) The placental barrier maintains steady state lithium concentration gradient between placental sinus plasma and fetal plasma. (b) In rabbits chronically treated with Li⁺ the steady state Li⁺ gradient is established within one hour after an acute Li⁺ loading, provided that the Li⁺ concentration in the maternal plasma is less than 4 mmole/l.