Monoclonal antibodies (MAbs) were raised in mice against acetylcholinesterase (AChE, EC 3.1.1.7) of the parasite Schistosoma mansoni. Specific tests were used, in which the hybridoma culture supernatants were screened for MAbs capable of recognizing AChE. The MAbs were characterized by their recognition of different stages of the parasite life cycle, by their binding to epitopes of protein or of carbohydrate, and by their capability of blocking AChE activity of the intact parasites. Furthermore, the MAbs were tested for their cross-reaction with AChE derived from various species. One of the MAbs, termed SA31, showed strong cross-reactivity with invertebrate and vertebrate species, indicating some similarity of cross-reaction between schistosome and mammalian AChE. However, most of the schistosome AChE epitopes are not shared with vertebrate AChE. The specific interaction of three other MAbs with intact schistosomula resulted in a marked complement (C)-dependent cytotoxicity. Specific schistosome AChE epitopes might be suitable candidates for drug design and vaccine preparation.