The efficacy of the trypanocides Samorin and Prothidium to protect beef cattle in areas of different trypanosome challenge was studied in Muabsa, Mozambique during an 18 month period. The performance of two groups of 1.5- to 3-year old bulls was observed, the first group in an area of high tsetse density, the second in an area of low to medium tsetse density. Glossina morsitans and G. pallidipes were present and their respective densities were determined using standard fly rounds, a mobile electric screen and biconical traps. The trypanosome challenge was determined using parameters of tsetse density and infection rates; the trypanosome risk was determined by Berenil Indices in both groups of animals. The Berenil Indices in the two study areas were not significantly different despite a great difference in apparent densities of the tsetse flies. The period of protection afforded by Samorin and Prothidium was similar in both areas which would appear to indicate that the tsetse density had no apparent effect on the degree of challenge. Samorin gave a slightly better protection than Prothidium as shown by a lower frequency of infections as well as higher packed cell volumes. There was no difference in growth rates between the treatment groups and study areas during the entire study period. It was concluded that in the study area Samorin usage is preferable to that of Prothidium. Tsetse densities obtained from standard fly rounds were found unsatisfactory in assessing the challenge, possibly because this method does not sample all components of the population. The Berenil Index, however, was found to be a useful indicator of trypanosome risk and thus frequency of treatment required.