Depressed patients show a characteristic decrease in the rate of uptake of serotonin into their platelets, which is normalised only by clinically effective antidepressant treatment. 2. We also find a decrease in platelet 5HT uptake rates in the olfactory bulbectomised (OB) rat model of depression, which return to normal following three weeks of treatment with desipramine or sertraline. 3. Synaptosomal 5HT uptake appears to consist of a low affinity, high capacity component and a high affinity, low capacity component, both of which are increased in the OB rat, compared to its sham operated control, and normalised by chronic antidepressant treatment. 4. The low affinity uptake of serotonin is not inhibited by in vitro incubation with sertraline, which suggests that the low affinity system may be associated with a non-specific uptake of 5HT into noradrenergic or dopaminergic nerve endings.