Rats were administered monoamine oxidase inhibitors [clorgyline, deprenyl, pargyline, or tranylcypromine] or serotonin uptake inhibitors [amitriptyline, chlorimipramine, nialamide or fluoxetine] for 1, 4 or 16 days. The binding of [3H]serotonin to brain homogenates and the concentration of serotonin in brain was measured. Treatments with inhibitors of serotonin uptake did not change the specific binding of [3H]serotonin in cerebral cortex or hippocampus, it did not produce any consistent changes in the concentration of serotonin in the cerebral cortex. Monoamine oxidase inhibitors capable of inhibiting A-type monoamine oxidase significantly decreased [3H]serotonin binding after both 4 and 16 days of treatment; serotonin concentrations were significantly elevated at all time intervals. Inhibitors of B-type monoamine oxidase had no effect on [3H]serotonin binding or serotonin concentrations in cerebral cortex. The reduction in labeled serotonin binding due to monoamine oxidase inhibitors is due to a decrease in the maximum number of specific binding sites with no change in the affinity of the binding sites for [3H]-serotonin.