The 5-nitroimidazoles, MK-436 and fexinidazole dissolved in dimethylsulphoxide can be converted by the addition of hydroxypropylcellulose into gels which facilitates the ease and accuracy of administration. When these gels are used in combination with melarsoprol gel they are capable of curing experimental murine CNS-trypanosomiasis with a one-day treatment. The use of melarsoprol/MK-436 was more efficient than melarsoprol/fexinidazole gels. Thus while a single treatment with 0.1 ml 3.6% melarsoprol gel with 0.1 ml (14.3 mumol) fexinidazole gel cured the infected mice, the same dose of melarsoprol gel with 0.1 ml (4.0 mumol) of MK-436 gel was equally effective. It was also possible to prepare a combined melarsoprol/MK-436 gel which cured experimental CNS-trypanosomiasis with a single treatment. Topical treatment with this melarsoprol/MK-436 gel mixture also resolved clinically the hind leg paralysis which is associated with post-treatment reactive encephalopathy caused by non-curative treatment of CNS-trypanosomiasis.