Two trials were carried out in order to compare the prophylactic effect of a subcutaneously implanted sustained release device (SRD) containing a mixture of a biodegradable copolymer, poly(caprolactone-co-L-lactide), and isometamidium (ISMM) with that obtained after intramuscular injection of the drug. In a first experiment under controlled conditions, two groups of cattle were treated with 0.5 mg/kg isometamidium either as a SRD or intramuscularly (i.m.), and exposed at monthly intervals to Glossina morsitans morsitans infected with Trypanosoma congolense. The average protection period was at least 24 months in the SRD treated against 5.7 months in the i.m. treated group. Using an ISMM enzyme-linked immunosorbent assay, the drug could be detected until 140 days post-treatment in the latter group, whereas in the former group, traces of the drug were detectable until 330 days after treatment. Furthermore, a field trial was carried out at the Madina Diassa ranch in Mali involving three groups of N'Dama cattle, each containing 23 or 24 animals. Two groups were treated with 1 mg/kg ISMM either as a SRD or i.m. and a third group served as untreated control. Twelve months after treatment, the cumulative infection rates were 56.5, 87.8 and 91.6% in the SRD implanted, the i.m. treated and the control groups, respectively. The ISMM concentrations were slightly lower than in the laboratory trial, but the overall pattern of drug disappearance from the sera of the SRD treated cattle was very similar in both trials. Statistical analysis showed that the incidence of trypanosomiasis was significantly lower in the SRD treated than in the i.m. treated group.