Liposomal encapsulation can limit passage of a drug from a peritoneal administration site to blood, while enhancing lymphatic transport. We evaluated the effects of liposome size on lymphatic transport after intraperitoneal administration. Liposomes tested had mean diameters of either 0.72, 0.46, 0.17, or 0.048 micron and identical compositions. [14C]Sucrose was the aqueous space marker (model drug). Doses were given to thoracic-duct-cannulated rats. The subsequent 0-5 h time-course of carbon-14 was quantified in thoracic lymph, several lymph nodes, blood, and urine. Calibration studies indicated a maximum of approximately 30% of the absorbed dose could be collected in thoracic lymph. Carbon-14 levels in the various nodes covered a 1000-fold range, and relatively high levels were observed in the left mediastinal, parathymic, cisternal, and renal lymph nodes. Liposome stability in vivo and in vitro increased with decreasing size. Absorption from the peritoneal cavity was independent of size. The smallest liposomes were collected in lymph with little lymph node retention. The largest liposomes were retained most by lymph nodes, and would be the best prototypical carrier of the group if increased therapeutic availability within both lymph and lymph nodes is desired. The results implicate other, unexplored physical and physiological variables as potentially of equal importance.