PURPOSE: To compare the lymphatic transport and the portal absorption of halofantrine (Hf) when administered in (i) a triacylglycerol (TG) solution, (ii) an o/w-emulsion that contains a metabolizable surfactant, and (iii) an o/w-emulsion that contains a synthetic surfactant. METHODS: Lymph cannulated rats were orally dosed with Hf in a TG solution or in o/w-emulsions dispersed by lecithin or Cremophor RH40. Lymph was continuously collected, and blood was sampled periodically in the course of 30 h. Hf in the lymph and blood and TG and phosphatidyl choline (PC) in the lymph were analyzed. RESULTS: A significantly (p < 0.05) higher level of Hf was found in the intestinal lymph when dosed in one of the emulsions (22.8+/-2.8% and 20.2+/-2.5%) compared to in the TG solution (7.9+/-1.1%). No difference in the lymphatic transport of Hf was observed between the two emulsions. The portal absorption of Hf was similar for the three vehicles. CONCLUSIONS: The emulsified vehicles favor an increased lymphatic transport of Hf. The portal transport of Hf was not significantly different for the three vehicles. This indicates that a different degree of dispersion of the TG vehicle can change the route of transportation of Hf.