The human platelet, which takes up and releases dopamine, has been proposed as a peripheral model for the study of dopaminergic neurons in the central nervous system (CNS). In addition, the platelet has been shown to possess membrane components with pharmacological properties similar to the dopamine-D1 (DA-D1) and D2 and (DA-D2) receptor on dopaminergic neurons. We have therefore studied the specificity of the platelet uptake system for dopamine and, as dopamine uptake comprises both internalised and membrane bound dopamine, the contribution of the DA-D1 and DA-D2 receptor to the uptake of dopamine has been assessed. Significant uptake of 3H-dopamine by platelet rich plasma (PRP) occurred after 10 min incubation at 37°C, uptake being maximal after 90 min. In contrast, at 4°C no uptake of 3H-dopamine occurred up to 60 mins incubation but at 20°C was approximately 8% of the 60 min uptake at 37°C. The neurotransmitters serotonin and dopamine inhibited dopamine uptake by platelets in a dose dependent manner. Uptake of dopamine appeared to be via two systems, one of high affinity with low capacity and the other of lower affinity but high capacity. In contrast, noradrenaline, adrenaline, acetylcholine, gamma-aminobutyric acid and histamine (10uM) had no effect on dopamine uptake by platelets. The DA-D1 receptor antagonist SCH 23390 (10um) and the DA-D2 receptor antagonists (10uM) spiperone, domperidone and (+)-butaclamol did not significantly affect dopamine uptake by platelets. In addition, ouabain and desipramine (100uM) inhibited dopamine uptake by 21% and 24% respectively whilst reserpine and imipramine (100uM) increased uptake by 14% and 15%. We therefore conclude that platelets take up dopamine via a selective, temperature dependent mechanism. Our data also suggest that dopamine uptake by platelets does not involve the DA-D1 or DA-D2 receptor.