Interest in the nematode polyprotein allergens/antigens (NPAs) originally arose because they were often found to be immunodominant antigens of nematode parasites, and in some cases also potent allergens. Quite separately, they attracted attention as the 'ladder' proteins found close to the surface of filarial nematodes. Screening of cDNA expression libraries with antibody from infected humans or domestic animals continues to reveal more NPAs. The search for the biochemical function(s) of NPAs was originally hampered by the lack of amino acid sequence similarities between NPAs and proteins of known function, but much is now known about their biochemical activity, the highly unusual means of their biosynthesis and their gene structure. Here, Malcolm Kennedy provides an update on these intriguing proteins.