The full-length cDNA sequences of three variable surface glycoproteins from bloodstream forms of Trypanosoma congolense have been determined. They encode preproteins of 429, 449, and 428 amino acids. These proteins contain the typical N-terminal leader sequences of secreted eukaryotic proteins, and display hydrophobic amino acids at their C-termini characteristic of variable surface glycoproteins; these leader sequences serve as transient membrane anchors after protein synthesis. By performing sequence comparisons of all currently known variable surface glycoproteins from T. congolense, several conserved elements could be identified. These elements included positional conservation of most of the cysteine residues, conservation of the flanking sequences surrounding these cysteine residues, clustering of proline residues near the C-termini, and a hydrophobic heptad motif near the end of the N-terminal domains. The N-terminal domains seem to be closely related to the B domains of Trypanosoma brucei variable surface glycoproteins, whereas the C domains have up to now only been identified in T. congolense variable surface glycoproteins. The data suggest that T. congolense variable surface glycoproteins, despite low sequence similarities, could have conserved tertiary structures.