1. This study investigates S-adenosyl-L-methionine (SAM) (10 mg/kg, i.p.)acute effects upon 5-HT metabolism in rat brain areas. 2. One hour after SAM injection 5-HT biosynthesis was increased in the corpus striatum (55%), the hippocampus (3-fold) (82% 2 hr after SAM injection) and decreased in the olfactory bulbs (34%). 3. 5-HT levels were: (a) increased in the corpus striatum (39%), the hippocampus (44%) and the frontal cortex (27%), and oppositely reduced in the olfactory bulbs (47%) 1 hr after SAM injection; (b) increased in the hippocampus (39%) and reduced in the olfactory bulbs (35%) 1.5 hr after SAM injection; (c) increased in the hippocampus (25%) 2 hr after SAM injection. 4. 5-HIAA levels were reduced in the olfactory bulbs 27% or 21% after 1 hr or 1.5 hr from SAM injection respectively. 5. These area-related changes in 5-HT biosynthesis and metabolism might suggest a possible neurochemical substrate for the antidepressant properties of SAM.