The epidemiology of bovine trypanosomosis was investigated in two districts (Savelugu and West Mamprusi) of Northern Ghana with different land use and environmental characteristics. The land use intensity and environmental change was suspected to be higher in the Savelugu District. A cross-sectional entomological survey conducted along the White Volta river and its tributaries confirmed the presence of only Glossina palpalis gambiensis and G. tachinoides. The challenge index as measured by the product of tsetse density and tsetse infection rate was much higher in the West Mamprusi (19.6) than in the Savelugu district (4.7). A total of 1013 cattle (508 in Savelugu and 505 in West Mamprusi) were bled from a random selection of 16 villages in the Savelugu District and 13 villages in the West Mamprusi District. Blood samples were examined for trypanosomes by the buffy coat technique (BCT). Blood samples that were positive in the BCT or negative in the BCT but with packed cell volume (PCV) values below 21 were further tested with a polymerise chain reaction for trypanosomal DNA. Plasma samples of all cattle were serologically tested with an indirect ELISA for trypanosomal antibodies. The parasitological and serological prevalence of bovine trypanosomoses was significantly higher in West Mamprusi (16 and 53%, respectively) than in Savelugu District (8 and 24%, respectively). An evaluation of animal health at the village herd level, using PCV as an index of anaemia, provided various epidemiological scenarios prevalent in the entire study area. © 2004 Elsevier B.V. All rights reserved.