Subclavian catheter (SCC) related infections are a major cause of morbidity in hemodialysis patients, the vast majority due to staphylococci species. Povidone-iodine (PI) has proven anti-staphylococcal activity. Therefore, a randomized controlled trial of topical PI ointment was undertaken to evaluate the impact of this prophylactic intervention on the incidence of SCC related infections in hemodialysis patients. The role of S. aureus nasal carrier state in the acquisition of infection was also evaluated. Patients requiring SCC for temporary hemodialysis access were randomized to receive the treatment (T; N = 63) or sterile gauze dressings alone (C; N = 66). Catheter duration ranged from 2 to 210 days in both groups, with a mean of 38.6 days in T and 36.2 days in C (NS). Exit site (ES) infections were significantly less in T (5%) versus C (18%) (P less than 0.02); tip colonization (TC) was 17% in T versus 36% in C (P less than 0.01), while the incidence of septicemia (S) was also significantly less in T (2%) versus C (17%; P less than 0.01). S. aureus nasal carriers were at a threefold higher risk of SCC related septicemia (0.009/day) than noncarriers (0.003/day; P less than 0.05). The beneficial effect of PI ointment was most evident in this high risk group of S. aureus carriers: ES = 0% T versus 24% C, TC = 12% T versus 42% C, S = 0% T versus 29% C, P less than 0.05. There were no adverse effects of the treatment. The routine application of topical PI ointment to temporary hemodialysis catheter exit sites is effective in reducing SCC related infections.