A study was conducted between January 2003 and June 2004 on 19,082 carthorses in 28 towns in Ethiopia to investigate the epidemiology of equine histoplasmosis (EH). Clinical and microscopic examinations were used and an overall prevalence of 18.8% (3579/19082) was recorded. Statistically significant (P<0.001) differences was observed in the average prevalence with high, medium, and low prevalence categories. The highest prevalence (39%) was recorded at Mojo while the lowest (0.0%) was recorded at five towns, namely, Agaro, Bokoji, Debre Berhan, Dinsho, and Sagure. The prevalence of EH was not associated (R=0.08, F=0.15, P=0.71) with the mean annual rainfall but was associated (R=0.64, F=11.5, P<0.01) with the average annual temperature. Statistically significant (R=0.57, F=12.34, P<0.01) association was observed between the altitude of the study towns and the prevalence of EH. Moreover, the number of cases of EH increased significantly (R=0.88, F=90.9, P<0.001) with the horse population in the towns. In general, EH was prevalent in hot and humid towns with an altitude ranging from 1500m above sea level (asl) to 2300masl but was nil or low in cold and in dry and windy towns. It was concluded that EH is prevalent in Ethiopia and warrants the initiation of a control strategy.