The organ distribution and half-life in blood of liposome-entrapped [14C]sucrose was examined in rats for two compositions of liposomes having widely differing drug release properties as determined by an in vitro assay in the presence of serum at 37 degrees C. The liposomes were composed of 1) egg phosphatidylcholine-cholesterol, 2:1 molar ratio and of 2) bovine brain sphingomyelin-phosphatidylcholine, 4:1 molar ratio. The two types of liposome were determined to have half-lives for release of contents in vitro in the presence of serum of 2.6 and 35 hr, respectively. Organ distribution and blood values were followed with time for small unilamellar, multilamellar and reverse-phase evaporation liposomes of both compositions. Free [14C]sucrose was almost totally eliminated from rats within 0.5 hr of injection. Liposome-entrapment increased the circulation time of sucrose in vivo in the following order: small unilamellar greater than reverse-phase evaporation greater than multilamellar liposomes. For all sizes of liposomes, the composition with slower leakage as determined by in vitro assay (sphingomyelin-phosphatidylcholine, 4:1) resulted in significantly longer half-lives in blood and in whole body. Liposomes containing sphingomyelin were taken up by liver to a lesser extent and by spleen to a greater extent than phosphatidylcholine-cholesterol liposomes of all sizes.