Screening 1154 ESTs from the plant-parasitic nematode Radopholus similis resulted in seven tags coding for proteins holding a transthyretin-like domain (PF01060). The seven ESTs corresponded to four different genes which were cloned from a cDNA library (accession numbers AM691117, AM691118, AM691119, AM691120). Transthyretin-like genes belong to a large family, different from the transthyretin and the transthyretin-related genes with whom they share some sequence similarity at the protein level. This similarity has caused an inconsistent use of different names and abbreviations in the past. To avoid further confusion, we introduce a standardized nomenclature for this gene family, and chose to name this barely characterized gene family ttl (as for transthyretin-like). Further examination of the identified genes, named Rs-ttl-1 to -4, showed that they are expressed in both juveniles and adults, but not in young embryos. Whole mount in situ hybridization revealed a distinct spatial expression pattern for two of the genes: Rs-ttl-1 is expressed in the tissues surrounding the vulva, whereas Rs-ttl-2 is expressed in the ventral nerve cord. The deduced protein sequences contain a putative signal peptide for secretion, pointing to an extracellular function of the mature proteins. Database screens showed that the ttl family is restricted to nematodes. Moreover, a HMMER search revealed that ESTs derived from ttl genes are more abundant in parasitic nematode libraries, with a bias towards the parasitic stages. Despite their abundance in nematodes, including the extensively studied model organism Caenorhabditis elegans, the function of TTL proteins remains obscure. Our data suggest a role in the nervous system. Even without insight into their biological function, the nematode-specific nature of this gene family makes it a promising target for nematicides or RNAi mediated control strategies against parasitic nematodes.