Increasing the pH of the spray water to solubilize the weak acid herbicide nicosulfuron and then decreasing pH below its pKa so that it converts into a neutral form enhances biological activity under some conditions. The water-dispersible granule formulation of nicosulfuron starts as dispersed particles. Adding 1% wt/wt K3PO4 solubilizes nicosulfuron and increases its activity compared to its dispersion without base. The type of buffer and the surfactant HLB or hydrophilic lipophilic balance, a measure of the molecular balance of the hydrophilic and lipophilic groups, altered the activity of nicosulfuron. Adding 1% wt/wt K3PO4 increases the pH, and the optimum HLB ranged from 13 to 17 on large crabgrass. Adding 1% wt/wt H3PO4 reduces the pH and lowers the optimum HLB range from 10 to 14 on large crabgrass. Adding the acidic buffer converts the solubilized nicosulfuron into its neutral form and increases activity under some surfactant conditions. Thus, neutral nicosulfuron is more active with lipophilic surfactants, while ionic nicosulfuron is more active with hydrophilic surfactants. When tested on other species, low HLB surfactants are the most active at low pH. These results support the concept that the physicochemical properties of the herbicide, adjuvants, and weed species should be matched for optimum activity.