SPL7013 is the sodium salt of a sulfonated dendrimer that has potent antiviral properties. VivaGel, a topical gel containing 3% (wt/wt) SPL7013, is in development as a vaginal microbicide. BufferGel is a Carbopol-based acidic buffering gel that enhances the natural protective action of the vagina to produce a broad-spectrum microbicidal environment. The positive attributes of both gels were combined into a combination vaginal microbicidal gel having dual mechanisms of action. A 3% (wt/wt) SPL7013 combination gel, pH 3.7, was developed and fully characterized and was shown to have more than twofold greater acidic buffering capacity than BufferGel. Ultracentrifugation experiments demonstrated that SPL7013 was not sequestered or entropically trapped in the viscous gel, thereby confirming, along with viral challenge studies, that SPL7013 has sufficient mobility in the viscous gel to exert antiviral properties.