A protein encoded by cDNAs from the human parasite Onchocerca volvulus and its homologs from Caenorhabditis elegans and Ancyclostoma caninum define a family of aspartic proteases that are most closely related to cathepsins D, but differ from them in lacking the N-glycosylation site known to be required for lysosomal targeting. The nematode proteins have a potential N-glycosylation site at the same position as mammalian cathepsins E and in common with these have atypically long N-terminal extensions. The literature implies that cathepsins E may be secreted, and adult female O. volvulus are known to secrete a specific inhibitor of aspartic proteases; we therefore predict that the protease is secreted as an enzyme-inhibitor complex.