Human platelets possess high-affinity ³H-imipramine binding sites. A study in ten healthy volunteers showed that platelet preparations produced by mechanical disruption contained varying proportions of intact platelets, as measured by the cytoplasmic marker enzyme LDH. This may invalidate the protein reference. Higher proportions of membranes in the preparations lead to higher B _max values of imipramine binding (fmol/mg protein). The use of intact platelets in imipramine binding studies is therefore preferable to membrane preparations, particularly in studies where the interindividual variation of binding parameters is of interest.