The effect of the liposome dose of bovine brain sphingomyelin/cholesterol (2/1; mol/mol) small unilamellar vesicles (mean diameter 187 42A) on the rate of elimination of the vesicles from the circulation of mice was investigated. The results of the study indicated that the relative rate of elimination of the vesicles from the blood depended on the amount of intravenously administered liposomal lipid. The distribution of the liposomes in vivo was followed by monitoring entrapped In-111. In all tissues examined, the uptake of the liposomes was a dose-dependent process. An examination of the dose dependency of the distribution of the administered liposomes in the blood and liver at 23 hours post-injection, and of the kinetics of the elimination of these vesicles from the blood, suggests a hepatic uptake process involving two parallel pathways. One pathway is apparently a capacity-limited Michaelis-Menten process; the other pathway is a linear, non-saturable process. These pathways operate in parallel but respectively dominate at the low end and the high end of the dose range examined.