Trypanosoma brucei is a blood-borne pathogen that changes its variant surface glycoprotein coat, thus evading immune destruction. Restriction digestion, combined with probe hybridization studies, was used to construct long-range restriction maps of the 1.4 (M4) and 1.5 megabase (M3) chromosomes from the IsTaR1 serodeme of T. b. brucei. Comparison of the two chromosomes suggests that they are a homologous pair. Hybridization with a repetitive sequence probe also identifies several copies on the M4 chromosome and a relative paucity of cross-hybridizing repetitive sequence on the larger M3 chromosome.