The membrane of eukaryotic cells represents a barrier normally imperme
able to non-lipophilic substances. In consequence, internalization of
extracellular compounds requires the presence of specific channels, or
of specialized endocytic mechanisms. Recently, several groups have re
ported that some growth factors and transcription factors can be inter
nalized by cells in culture and addressed to the cytoplasmic and nucle
ar compartments. In the latter case, they have been shown to interfere
directly with gene transcription. Among these factors are fibroblast
growth factor-1 and -2 (FGF-1 and FGF-2), schwannoma-derived growth fa
ctor (SDGF), Tat protein and homeodomain or homeodomain containing pol
ypeptides. In the present paper, we present the available data concern
ing these unconventional uptake mechanisms and speculate on their pote
ntial interest to target macromolecular structures into live cells.