AbstractChlorimipramine, fluvoxamine and fluoxetine are clinically effective in obsessive‐compulsive disorder (OCD) and inhibit serotonin (5‐HT) reuptake. There are as yet no validated animal models for OCD. Therefore evidence for clinical efficacy in this illness has to be deduced from various preclinical tests. Different animal models for ‘anxiety’ clearly differentiate between the serotonin uptake inhibitors and the classical anxiolytics such as the benzodiazepines, drugs not very effective in the treatment of OCD. One animal ‘anxiety’ paradigm, ultrasonic distress calls in rat pups, appears as an attractive model to differentiate various anxiolytic agents and should be considered as a tool to detect putative anti‐OCD properties of drugs. The neurochemical profile of the selective 5‐HT uptake inhibitors such as fluvoxamine and fluoxetine obviously leaves very little room for alternative mechanistic hypotheses about the mechanism of action of their clinical efficacy, not only in OCD, but also in depression. It is speculated whether certain receptor types, notably 5‐HT1Creceptors, are particularly involved in the