Syringomycin E (SR-E), a new antifungal produced by the bacterium Pseudomonas syringae pv. syringae, was evaluated in a murine vaginal candidiasis model. In one study, mice were treated intravaginally b.i.d. for 4 days with drug carrier, SR-E 2% in either PEG-400 or PEG-ointment, or 1% clotrimazole as a positive control. Quantitative vaginal cultures were taken prior to treatment on day 1 and on days 5, 6, and 7. Both formulations showed a reduction of yeast colonization in the vaginas on day 5 (P ≤0.06 and P ≤0.03 for SR-E/PEG-400 and SR-E/PEG ointment, respectively) and SR-E/PEG ointment reduced the colonization on day 7 (P ≤0.06) when compared to carrier treated controls. In a second study, SR-E was formulated in Aquaphor at three higher concentrations of SR-E [3%, 6%, or 12% (w/v)]. SR-E showed dose-dependent efficacy. The 3% dose showed no effect while the 6% and 12% doses reduced the number of yeasts. The 12% dose showed a significant reduction on days 5 (P ≤0.01), 6 (P ≤0.06), and 7 (P ≤0.03) when compared with the drug carrier controls and on day 5 was more effective than clotrimazole (P ≤0.03). Clotrimazole did not significantly reduce the yeasts in the vagina until days 6 (P ≤0.01) and 7 (P ≤0.01) when compared to the drug carrier controls. No vaginal inflammatory response was evident by histological examination in uninfected animals treated with SR-E. No SR-E could be detected in plasma, kidney, or liver. SR-E (12%) was an effective treatment when compared to 1% clotrimazole.