Sixty-eight health care workers were enrolled in a double-blind clinical trial and randomized to receive either mupirocin calcium ointment or placebo, intranasally bid for 5 days. Nasal cultures were taken immediately before starting treatment, 1 and 2 during treatment, at the end of treatment, 3 days later, weekly for 1-5 weeks and then monthly for 2-6 months after treatment. Mupirocin eliminated nasal carriage with Staphylococcus aureus in 58% of subjects within two days and 86.7% subjects by the end of therapy compared to 9.4% subjects at the end of treatment with placebo (P < 0.001). Post-treatment colonization rates of 43%, 56% and 67% were attained after 1 month, 2-4 and 6 months treatment with mupirocin respectively and recolonisation with the same strain of S. aureus that had been isolated before treatment was noted in 32%, 40% and 48%. No resistance to mupirocin developed and the drug was well tolerated. Mupirocin is safe and effective in suppressing nasal carriage of S. aureus.