Past in vitro functional assays have demonstrated that platelet function is not inhibited by liposome uptake. In the present study, the organ distributions of control and liposome-loaded Sprague-Dawley rat platelets were examined to determine whether liposome uptake enhances RES uptake. Platelets were isolated using STRactan density gradient centrifugation, incubated with small unilamellar liposomes in vitro for 1 hour, labeled with 51Cr and injected into a cohort group of rats. One hour post-injection the spleen, liver, lungs, blood, kidneys and bladder contents were removed and the percentages of the recovered dose localized per total organ (%RD) were determined. The RES index, defined as %RDliver + %RDspleen, were 24.8 +/- 4.5 and 20.5 +/- 5.0 for the control platelets and liposome-loaded platelets, respectively. These results indicate that liposome uptake does not enhance RES uptake.