We have previously reported on the cloning of the 14-3-3 protein of Schistosoma mansoni. Here, we evaluate the potential use of this protein as a vaccine candidate against infection by S. mansoni Sm14-3-3 was expressed and purified either as a free protein or as a fusion protein to SjGST or MBP. Sera from mice infected with S. mansoni recognized both SjGST and 14-3-3 indicating that antibodies against these two proteins are induced in the course of the natural infection. Furthermore, mice immunized with either 14-3-3, GST or 14-3-3-GST; reacted with cercaria lysate. A cellular immune response was also detected particularly in mice immunized with 14-3-3-GST: With respect to the effect on biological functions, antibodies to 14-3-3 and 14-3-3-GST caused 23-32% complement-mediated cytotoxcity of S. mansoni schistosomula compared to only 10-11% induced by either normal mouse serum or GST alone. In challenge infection with S. mansoni, immunization with 14-3-3, either as a fusion protein or as a free protein, led to protection ranging from 25-46%, as determined by reduction of adult worm burden, while SjGST alone elicited only 0-8% protection and MBP alone did not elicit any protection.