Amphotericin B is administered as a colloidal suspension due to its insolubility in water. Macrophap, particularly those in the liver, have been implicated as the predominant all type responsible for the uptake of colloidal amphotericin B. We examined the effect of infusion time and macrophage function to confirm the role of the macrophage in the uptake of amphokrian B. Prolonged infusion time (24 h compared to 6 h) resulted in significantly less hepatic and splenic accumulation of amphotericin B. Blockade of macrophage function with methylpalmitate also resulted in sigruficantly decreased hepatic and splenic uptake of amphotericin B. Uptake of amphotericin B by lung macrophages was not significantly affected by methylpalmitate. The area under the serum concentration versus the curve was significantly higher in the group that received methylpalmitate compared to either the 6 or 24 h amphotericin B infusion groups. These results suggest that fixed macrophages play an important part in the pharmacokinetics of amphotericin B, and that increasing drug solubility may alter the pharmacokinetics of amphotericin B.