A single dose of LiCl (2-4 mmol/kg) administration to adult male albino rats produced no significant effect in (a) steady-state level of tryptophan (Trp), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), (b) pargyline-induced 5-HT accumulation and declination of 5-HIAA, (c) probenecid-induced 5-HIAA accumulation and (d) MAO activity in any region of brain. Long-term treatment (for 7 consecutive days) with LiCl (2.0-4.0 mmol/kg/day, p.o.)increased (a) steady-state level of Trp (29.4-53.2%), 5-HT (20.2-35.0%) and 5-HIAA (30.0-65.0%), (b) pargyline-induced accumulation of 5-HT (50.6-120.2%) and declination of 5-HIAA (41.9-85.2%), (c) probenecid-induced accumulation of 5-HIAA (41.9-85.2%) and (d) mitochondrial monoamine oxidase (MAO) activity (26.2-36.1%) in brain H and PM. Extension of the period of treatment to 14 consecutive days with LiCl at a dose of 2.0 mmol/kg/day failed to produce any appreciable change in the above parameters of 5-HT metabolism in any of the brain regions of rat brain. Administration of LiCl at a dose of 4.0 mmol/kg/day for 14 consecutive days, on the other hand, decreased the level of Trp (21.5-34.2%), 5-HT (25.1-34.5%), 5-HIAA (12.0-20.0%), pargyline-induced accumulation of 5-HT (23.8-35.5%) and declination of 5-HIAA (20.0-34.2%) and probenecid-induced accumulation of 5-HIAA (20.2-35.1%) in H, ST and PM. But the MAO activity was increased in these regions under similar conditions. Further prolongation of treatment with LiCl (2.0 and 4.0 mmol/kg/day, p.o.) for 21 consecutive days produced a greater effect on the above parameters in H, ST and PM. These results suggest that LiCl produces region specific differential action depending on its dosage and the duration of treatment in serotonergic activity in brain.