BACKGROUND: Existing data on human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense among children are limited. Here, we described the demographic, clinical, diagnostic, treatment and outcome characteristics of HAT in pre-school children from Kajo-Keji County, South Sudan in comparison with older patients. METHODS: We did a retrospective analysis of HAT patients treated at the Kiri Sleeping Sickness Treatment Centre (SSTC), Kajo-Keji County, from June 2000 to December 2002. RESULTS: Of 1958 HAT patients, 119 (6.1%) were pre-school children (<6 years) including 56 (47%) in first-stage illness and 63 (53%) in second-stage. The proportion of children in second-stage HAT was significantly higher in very young children (<2 years). Walking and speech disturbances were more frequent in second-stage HAT but other neurological symptoms and signs were not associated with disease stage. Pentamidine treatment for first-stage illness was very safe and effective among pre-school children. In contrast, 4.9% of pre-school children in second-stage illness died during melarsoprol treatment and 46% had > or = 1 severe adverse event(s). Macular rash, jaundice and skin necrosis on injection site were significantly more frequent in this age group (p<0.05). Melarsoprol-induced encephalopatic syndrome was less frequent but more severe than in older age groups. CONCLUSION: The clinical features of T. b. gambiense HAT among pre-school children are insufficiently stage-specific. Therefore, laboratory-based staging is mandatory to prevent unnecessary harm to HAT patients caused by the high toxicity of melarsoprol.