Aminoacyl-tRNA synthetases of higher organisms are far less studied compared to their prokaryotic and unicellular eukaryotic counterparts. However, many aminoacyl-tRNA synthetases from multi-cellular organisms exhibit certain features not yet described for the same enzymes of bacteria or yeast. Tryptophanyl-tRNA synthetases (TrpRS) are among the most thoroughly studied mammalian enzymes of this group. TrpRS are Zn(2+)-dependent, dimeric, class I aminoacyl-tRNA synthetases with known amino acid sequence for four different mammalian orders. TrpRS is not associated in a stable multi-synthetase complex, although it exhibits a long N-terminal extension absent from bacterial TrpRS. The human gene encoding TrpRS belongs to the interferon-responsive gene family and TrpRS activity drastically increases after interferon gamma induction. For unknown reasons TrpRS is overproduced in pancreas of Ruminantia. Other data on TrpRS available so far are summarized and briefly discussed here.