We describe a patient with chronic depression who was treated with the selective serotonin-reuptake-inhibitor sertraline. Following surgery, the patient developed severe nausea and vomiting, necessitating an efficient antiemetic treatment, possibly including the 5-HT3-receptor antagonist ondansetrone. Because both drugs, sertraline and ondansetrone, interact with the serotonin system at the synapsis, a possible interaction was discussed. Since the effect of the selective serotonin-reuptake inhibitors mainly depends on 5-HT1 and 5-HT2-receptors, a pharmacodynamic interaction between an 5-HT3-antagonist and a serotonin-reuptake-inhibitor at the synapsis leading to the relapse of depression seems to be very unlikely. There exist also no conclusive data suggesting a clinically relevant pharmacokinetic interaction between the two drugs. A treatment with ondansetrone was considered to be safe in this patient.