Domains have been identified in the Gag proteins of a number of retroviruses, and in the matrix proteins of the rhabdoviruses and filoviruses, that play a critical role in the pinching off of virus particles from the plasma membrane. These sequences are collectively termed late or L domains to reffect their function late in the virus budding process. One of the intriguing features of these L domains is that they all contain highly conserved motifs known to mediate protein-protein interactions between cellular proteins. Three classes of motifs have been defined in viral L domains: PTAP, PPXY, and YXXL. In each case, the integrity of these motifs appears to be essential for L domain activity, suggesting that L domains function by interacting with a host factor (s). This minireview summarizes the present state of our knowledge concerning viral L domain function and describes recent tantalizing clues regarding the identity of the cellular partners with which L domains interact. Retroviral Gag proteins are synthesized as polyprotein precursors that are cleaved by the viral protease (PR) during or shortly after release from the cell. Although sequence conservation between the Gag proteins of different retroviral genera is very limited, all retroviruses, with the exception of the spumaretroviruses, encode three major Gag domains: matrix (MA), capsid (CA), and nucleocapsid (NC)(for reviews, see references 15, 16, and 74). In addition to these well-characterized domains, which are invariably ordered MA-CA-NC in the Gag precursor, a variety of additional domains and spacer peptides with diverse functions are encoded by the gag genes of individual retroviruses. Expression of retroviral Gag precursor proteins is both necessary and sufficient for the assembly and release of noninfectious, virus-like particles; Gag processing by PR is not required for particle production. Retroviruses have evolved several mechanisms for particle assembly and release (for reviews, see references 21 and 74). For those viruses that use the so-called C-type pathway (eg, alpharetroviruses such as Rous sarcoma virus [RSV], gammaretroviruses such as murine leukemia virus [MLV], and lentiviruses such as human immunodeficiency virus type 1 [HIV-1]), particle assembly occurs at the plasma membrane. In contrast, betaretroviruses (eg, mouse mammary tumor virus and Mason-Pfizer monkey virus [M-PMV]) use the B/D-type pathway, in which particles assemble in the cytosol and are then transported to the plasma membrane. For both C-and B/D-type retroviruses, budding occurs from the plasma membrane and L domains have been defined for both classes of retroviruses. Intracytoplasmic A-type particles and spumaretroviruses bud primarily at intracellular membranes and will not be discussed further, since L domains for these viruses have not been characterized. Regardless of the assembly pathway, virus budding from the plasma membrane requires a membrane fusion or pinching-off event. As is the case for the membrane fusion step in virus entry, this fusion reaction likely involves a complex interplay between viral and host factors.