The potential of a recombinant Schistosoma bovis-derived glutathione S-transferase (rSb28GST) to protect cattle against S. mattheei infection was tested in Zambia. All animals were challenged 2 weeks after the second inoculation with either 0·250 mg rSb28GST in adjuvants (vaccinated calves, n=14) or adjuvants alone (controls, n=14). In a first experiment, 7 vaccinated and 7 control animals were exposed to 10000 S. mattheei cercariae percutaneously. All animals developed clinical schistosomiasis 7–8 weeks after challenge. At perfusion, 12 weeks after challenge, vaccinated and control groups had averages of 887 and 541 eggs per gramme (epg) faeces, 6515 and 5990 worms, and 4·2 and 3·4 million tissue eggs, respectively. These results indicate that the immunization protocol used did not protect these calves against the massive single experimental challenge. In a second experiment, another 2 groups (n=7) of vaccinated and control animals were challenged naturally over a period of 9 months on a farm known to be endemic for S. mattheei. The natural infections were much lighter in intensity, as indicated by the mean faecal egg count (13 epg), worm count (139) and tissue egg count (294000) in non-vaccinated controls. In vaccinated calves, significant reductions in female worm burdens (50%), faecal egg counts (89%) and miracidial counts (93%) were recorded. Total tissue egg counts were also reduced by 42% in vaccinated animals. It therefore appears that the rSb28GST can provide significant protection in cattle against S. mattheei under conditions of low to moderate natural infection.