The cellular uptake of the phosphonylmethoxyalkylpurine derivatives HPMPA and PMEA has been studied in H9 cells. The two compounds exhibited an identical pattern of permeation in this cell line. Uptake did not occur via the nucleoside transport system, but through a different mechanism which, for its slow kinetics and temperature-dependence, is compatible with an endocytosis-like process. The amount of cell-associated drug increased up to one hour post-incubation.