We have studied the efficacy of topical Mupirocin for elimination of Staphylococcus aureus (Staph. aureus) nasal carriage in CAPD patients. Staph. aureus nasal carriers in our CAPD program were randomized to one of two groups: Group 1, treated with Mupirocin, and Group 2, treated with neomycin sulphate nasal ointment. The prevalence of Staph. aureus nasal colonization was 44% for patients (24/54) and 17% for dialysis partners (5/29). Group 1 included 11 patients and 1 partner, and Group 2, 8 patients and 2 partners. In Group 1, the eradication rate was 100%, and the recolonization rate was 0, 8, 41, 55 and 66% at 1, 2, 3, 6 and 10 months. In Group 2, the eradication rate was 40%, with a recolonization rate of 0.25 and 75% at 1, 2 and 3 months. Re-treatment with mupirocin was successful in 66% of the cases, compared to 20% for neomycin. The MIC90 of mupirocin for Staph. aureus was 0.5 mcg/mL, with an increase to 4 mcg/mL towards the end of the study. During the study period, there was a very low incidence of Staph. aureus peritonitis or catheter-related infections in patients treated with mupirocin. Secondary effects of mupirocin were negligible. Mupirocin is more effective than neomycin sulphate for the elimination of Staph. aureus nasal colonization in patients undergoing CAPD. Periodic re-treatment is frequently necessary, given the significant recolonization rate.