Pilot in vitro studies demonstrated that nystatin combined with Silvadene (silver sulfadiazine 1% [Marion Laboratories, Inc., Kansas City Mo.]) or Furacin in a 1:1 ratio was equally effective against Candida albicans and ATCC strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, but Sulfamylon (Winthrop Pharmaceuticals, Winthrop, N.Y.) combined with nystatin demonstrated an antagonistic response. Therefore we examined the susceptibility to nystatin of 165 clinical isolates, both gram-positive and gram-negative, to nystatin combined with Silvadene or Sulfamylon and 144 isolates to nystatin and Furacin. Both Silvadene and Furacin combined with nystatin were equally effective against the microorganisms as were the individual drugs. Conversely, Sulfamylon combined with nystatin lost its antimicrobial capability (93.3% resistance, p less than 0.001). On the basis of the in vitro results, 93 patients with acute burns were treated with the appropriate topical antimicrobials from April 1988 to September 1988. Of the 93 patients treated, 90 had neither a major systemic bacterial nor a Candida sepsis, and none of these patients had associated localized burn wound sepsis during their hospital stays. These 90 patients were discharged without any documented signs of infection. The average burnsize was greater than or equal to 29.44% total body surface area. These data suggest that the antimicrobial properties of nystatin, when combined with Silvadene and Furacin, remain effective. Consequently, such combinations have been effective in controlling both local and systemic Candida and bacterial burn wound sepsis.