The measurement of steady state levels of 5-HT and 5-HIAA, monoamine oxidase (MAO) activity, probenecid-induced accumulation of 5-HIAA, pargyline-induced accumulation of 5-HT and pargyline-induced declination of 5-HIAA in hippocampus of theophylline (Th) nontolerant [single or 4 consecutive days of Th (10-20 mg/kg/day, p.o.) treatment], tolerant [Th (10 mg/kg/day, p.o.) treatment was continued for 16 consecutive days] and withdrawal [at 48th h following the development of Th tolerance] rats suggest that (a) the metabolic activity of hippocampal serotonergic system is enhanced in Th nontolerant rat which becomes normal during the development of tolerance to Th, (b) Th withdrawal enhances hippocampal serotonergic activity, and (c) hippocampal 5-HT is not involved in the regulation of Th-induced locomotor activity under its nontolerant, tolerant and withdrawal conditions.