Platelet function in 12 cancer patients was studied sequentially over 97 hr of interleukin-6 (IL-6) daily bolus or continuous infusion (C.I.) therapy. During this period, enhanced ex vivo agonist-induced platelet maximum aggregation (MA) was paralleled by an increase in plasma levels of TXB2and PF4 as measured by RIA and ELISA, respectively. Platelet-rich plasma (PRP) specimens from bolus IL-6-treated patients demonstrated an increased incorporation of actin-binding protein and myosin in the cytoskeletal core (triton insoluble residue) as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in comparison to control specimens. Similarly, the integrin glycoprotein IIIa (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. A significant decrease in hypotonic shock response (HSR) was observed over 87 hr of treatment in IL-6 C.I. patients, whereas in IL-6 bolus patients, a significant increase in HSR occurred immediately after the bolus, which was followed by a significant decrease in HSR after 23 hr. These results suggest that IL-6 alters platelet function in vivo.