We have previously reported the effect of a compound derived from estradiol containing a radical amino butyl at the 17-beta position which has shown anticoagulant effects in whole blood and antiplatelet effects in light transmission aggregometry where platelets are isolated from other blood cells. In contrast, whole blood aggregometry includes the platelet interactions with blood elements such as erythrocytes and leukocytes. We examined the cooperative effect between leukocytes, erythrocytes and platelets and the antiplatelet effect of Buame in whole blood aggregometry, a tool to assess platelet function in its physiological environment. Buame (5-500 microM) dissolved in DMSO was tested in platelet aggregation induced by ADP (1.25 microM) or collagen (1 microg/mL) and the response recorded over 5 min. Controls were run with DMSO and the average control aggregation was taken as 100%. Results were obtained in both whole blood and platelet aggregometry. Buame was able to inhibit the secondary aggregation induced with ADP suggesting impairment in thromboxane A2 production. Also the first and second aggregation phases were inhibited when collagen-induced platelet activation was employed. This concentration-dependent pattern was shown in both whole blood and platelet aggregometry assays. When tested in light transmission aggregometry, a higher concentration of Buame was required in order to inhibit to the same degree ADP- or collagen-induced platelet aggregation (30 microM ,114 microM) than that required in the whole blood assay (IC50 84 microM, 191 microM). Interactions among different cell types in whole blood may modify the response of Buame-treated platelets to agonists suggesting a cooperative mechanism.