Endocytosis of the fluid phase marker, horse radish peroxidase, into baby hamster kidney cells is inhibited by treatment of cells with the fungal metabolite wortmannin. The IC50 of approximately 5 nM is consistent with the well-described action of wortmannin upon phosphatidylinositol (PI) 3-kinase. Analysis of the kinetics of uptake indicates a > 50% decrease in the initial rate of marker internalisation, a concomitant decrease in the volume of the early endosome and an increased efficiency of recycling of that marker which is internalised. As PI 3-kinase binds to activated growth factor receptors our data suggest that receptor activation can be coupled to receptor internalisation (down regulation) by localising PI 3-kinase stimulation of endocytosis.