We tested two topical antimicrobial agents (TAAs), silver sulfadiazine and mafenide acetate, to determine their cytotoxic effects when human lymphocytes and neutrophils were incubated with the agents in vitro for 30 minutes. Dilute concentrations of both TAAs markedly inhibited neutrophil respiratory burst activity and mitogen-stimulated lymphocyte proliferation (p < 0.05). The components of silver sulfadiazine (silver and sulfadiazine) were separately tested, and each component inhibited both neutrophil and lymphocyte functions. Mafenide acetate markedly decreased intracellular Ca+2 flux in lymphocytes. The effects of the TAAs were partially reversed when cells were washed and resuspended in medium after they were exposed in vitro to the TAAs. Commonly used TAAs may contribute to local immune dysfunction in the patient with burns. Because evidence suggests that T lymphocytes may participate in wound healing, prolonged treatment with TAAs may also effect certain aspects of wound healing.