Dipyridamole has been reported to inhibit platelet aggregation in citrate anticoagulated whole blood (WB). However, citrate may alter the response of platelets and/or the effect of antiplatelet drugs. The present study evaluates the "ex vivo" effect of dipyridamole, two hours after a single dose (3 mg/Kg) in 25 normal subjects in non-anticoagulated (native) WB and in WB anticoagulated with citrate or hirudin. We have used the BASIC anticoagulated with citrate or hirudin. We have used the BASIC wave as analytical method, which can evaluate the early steps of platelet activation with collagen in less than 1 min after venoclysis, thus allowing the study in native WB. The results show that dipyridamole significantly inhibits (p less than 0.001) platelet activation to collagen in citrated WB (66%) while the drug's effect is much lower (21%) and non-significant if evaluated in native or hirudine anticoagulated WB. These results suggest that citrate or low calcium concentration amplify the drug's platelet inhibitory action in WB and, therefore, the laboratory results may overestimate the drug's effect "in vivo".