Liposomes are used as drug delivery systems to improve the efficacy and lower the systemic toxicity of loaded small molecule drugs. However, some liposomes (such as pegylated liposomal doxorubicin (Caelyx)) show sex-dependent pharmacokinetics, whereby they are cleared more slowly in females than in males. This can lead to enhanced toxicity in women compared to men. The clearance of Caelyx is associated with monocyte count whereas hormones can play an important role in driving the phagocytic activity of monocytes and macrophages. We therefore hypothesised that sex hormone concentrations may influence the clearance of Caelyx by macrophages and monocytes. In the present study, we compared the uptake of doxorubicin and Caelyx by human THP1 acute monocytic leukemia cells in presence and absence of sex hormones using flow cytometry and confocal microscopy. Estradiol (E2), but not testosterone, increased Caelyx uptake into THP1 cells, measured by following rhodamine-labelled phospholipids incorporated into the liposome structure and doxorubicin loaded in the liposomes. However, there were no differences in the uptake of doxorubicin in the presence and absence of E2. Neither doxorubicin nor Caelyx treatment induced THP1 cell differentiation into macrophages. Furthermore, the increase in Caelyx uptake following addition of E2 was not observed when the THP1 cells were differentiated into macrophages. Our findings indicate that E2 levels are important in determining the capacity of monocytes to internalise liposomes, but are unlikely to be a significant factor in driving observed sex differences in the pharmacokinetics of liposomes.