We have studied the kinetics, biodistribution, and fate of autologous platelets labeled with 111In-oxine in rabbits. The initial recovery was 75% and mean survival time was 2.8 days when the data were analyzed by the multiple-hit gamma function model. Using a modified geometric mean for correction of attenuation, there was good correlation between the values obtained by in vivo quantification and those obtained by postmortem measurements of the radioactivity in the liver and the spleen (i.e., r = 0.854 and 0.899, respectively, n = 32). Using this method, it was shown that after infusion, the 111In-platelets rapidly accumulated in these two organs reaching 35% and 12% of the injected dose in the liver and spleen, respectively, by 1 day. Thereafter, there was little subsequent change. On the sixth day, when essentially all of the 111In-platelets had cleared from the circulation, a total of 82% of the injected dose was deposited in the three major reticuloendothelial organs: liver (40%), spleen (14%), and bone marrow (28%). Our results suggest that in addition to liver and spleen, bone marrow played an important role in sequestering platelets in rabbits.