The nuclear envelope is strategically located between the nucleoplasm and cytoplasm, and, as such, can play a major role in controlling cellular activity by regulating the exchange of macromolecules between these two compartments. The nuclear pore complexes, which are located within circular areas formed by fusion of the inner and outer membranes of the envelope, represent the primary, if not the exclusive, exchange sites. Individual pores are able to function in both protein import and RNA efflux from the nucleus. Translocation of macromolecules occurs by either passive diffusion or facilitated transport through central channels within the pores. The functional size of the diffusion channel is approximately 9 to over 12 nm in diameter depending on the cell type. The width of the transport channel varies as a function of the number and effectiveness of the specific nuclear targeting signals contained within the permeant molecule. The maximum diameter of the channel can be over 26 nm. Nucleocytoplasmic exchanges can be regulated either by (1) differences in the properties of the transported molecule (molecular size and signal content) or (2) changes in the properties of the pore complexes, which can effect both diffusion and transport.