The treatment of Machado-Joseph disease (MJD) has so far been purely symptomatic. Encouraged by previous publications reporting some improvement in spasticity and gait in two patients with MJD treated with sulphamethoxazole and trimethoprim (Bactrim), we carried out a double-blind, placebo controlled cross-over trial in eight patients. Three kinds of parameters were used to evaluate the treatment effect: subjective performance, neurological examination and timed tests. The results showed that Bactrim had a beneficial effect on gait and coordination and that it would be worthwhile undertaking other trials, taking into account the great clinical variability of MJD.