Since 1988, the french non-governmental organisation Médecins Sans Frontières is running a control program of human african trypanosomiasis in the district of Moyo, North-Uganda. Between 1988 and 1993, more than 7,000 patients were diagnosed and treated. Since 1988, it has been noted that incidence of melarsoprol reaction had increased systematically between June and October of each year, indicating strong seasonal variation. In 1992 and 1993, two outbreaks of arsenical reactive encephalopathy (ARE) occurred in the sleeping sickness center of Adjumani. The incidence of ARE suddenly exceeded 10% of the patients treated by melarsoprol during August 1992 and September 1993. The onset of 80% of those "epidemic" cases, occurred between the 5th and the 11th day of treatment. Two retrospective studies were conducted in 1992 (75 cases) and in 1993 (51 cases). Among the risk factors studied, two appear to increase the risk of ARE: the prescription of thiabendazole to treat strongyloidiasis during the melarsoprol cure and the bad general clinical conditions of patients. These observations suggest that exogenous co-factors could be involved in the occurrence of ARE. Recommendations were to avoid administration of diffusible anti-helminthic treatment during the cure, and to improve the general conditions of patients before the cure of melarsoprol.