Whole blood serotonin (5-hydroxytryptamine, 5-HT) was assayed, and factors possibly influencing 5-HT content were investigated in healthy controls. No significant circadian rhythm or effect of dexamethasone or meals was observed. After use of fluvoxamine, a specific 5-HT reuptake inhibitor, the whole-blood 5-HT concentration of patients was strongly reduced. After treatment with tranylcypromine, an unspecific monoamine oxidase inhibitor (MAOI), the 5-HT content was increased. Determination of whole blood 5-HT in patients treated with fluvoxamine presents a measure of drug compliance. Furthermore, the method may have clinical potential for finding an adequate dose when a 5-HT reuptake inhibitor or an MAOI is used.