Calcium ions act as a second messenger to platelet agonists, with increases in intracellular calcium bringing about changes in shape, aggregation, and release reactions. Changes in platelet function have been reported previously in migraine sufferers and there is evidence that hyperaggregability occurs during a migraine attack. It was decided to assess platelet aggregation with platelet-rich plasma (PRP) from nicardipine-treated migraine sufferers because dihydropyridine derivatives are known to inhibit adenosine diphosphate (ADP)- and epinephrine-induced aggregation. Aggregation induced by 1.4 mumol/L arachidonic acid was similar in PRP from control subjects and untreated migraine sufferers, whereas 1 or 2 mumol/L ADP-induced aggregation was lower in PRP from migraine sufferers. Treatment with 20 mg of nicardipine three times daily for 2 months significantly (p less than 0.05) increased 2 mumol/L ADP-induced aggregation. It is concluded that nicardipine was acting either on migraine pathogenic mechanisms or directly on the platelets.