An unexpected inhibition of human platelet aggregation by dopamine -- the precursor of epinephrine and norepinephrine -- is presented. Human platelet-rich plasma was incubated in an aggregometer for 120 seconds at 37 degrees C, with either dopamine or saline control. Adenosine diphosphate, epinephrine or collagen was added as the aggregating agent. Dopamine inhibits induction of platelet aggregation by all three agents and causes platelet disaggregation. At low doses (400 mug/ml or less), dopamine induces platelet aggregation and enhances ADP-induced aggregation. In addition, a concentration of dopamine of 40 mug/ml induces aggregation, enhances ADP-induced aggregation and inhibits epinephrine aggregation. Phentolamine is able to block dopamine enhancement of ADP aggregation, but propranolol and haloperidol fail to prevent dopamine inhibition of epinephrine aggregation. These observations are explained neither by the currently known intracellular actions of dopamine which involve competition with serotonin nor by a single mediator such as cyclic adenosine 3':5'-monophosphate. It appears that dopamine may exert its effects via the platelet membrane.