Background.—Platelets are activated in patients with cluster headache, during both the remission period and the active cycles. Objective.—To delineate more clearly the origin of platelet activation in cluster headache. Methods.—Platelet aggregation induced by collagen (0.5 μg/mL and 2 μg/mL), adenosine diphosphate (10−5 M and 10−6 M), and platelet‐activating factor (10−6 M and 10−7 M) was determined by the Born's method in 26 patients with cluster headache and 24 sex‐ and age‐matched controls. Results.—The platelets of patients with cluster headache aggregated significantly less to collagen at a concentration of 0.5 μg/mL compared to those of controls (P  =  .04). The extent of platelet aggregation obtained with a higher dose of collagen (2 μg/mL) was in the same range in both groups. Platelet aggregation obtained via adenosine diphosphate at a concentration of 10−6 M was significantly reduced in patients with cluster headache in comparison to controls (P  =  .002), but no differences were found at a concentration of 10−5 M. In contrast, the platelets of patients with cluster headache aggregated significantly more to platelet‐activating factor at both the concentrations of 10−6 M (P  =  .001) and 10−7 M (P  =  .00001) compared to those of controls. Conclusions.—This study suggests that platelet aggregation is impaired in patients with cluster headache during the active phase of the disease. We found hypoaggregation in response to low doses of collagen and adenosine diphosphate, and hyperaggregation when platelets were stimulated with platelet‐activating factor. Any interpretation of these results can only be speculative. It may be that impairment of platelet aggregation with collagen and adenosine diphosphate may indicate a derangement of nitric oxide function, while the hypersensitivity to platelet‐activating factor may be due to fluctuations in its plasma levels.