AbstractScale reduction of chemical reactions enables novel screening and synthesis approaches that facilitate a highly parallelized and combinatorial exploration of chemical space. Droplet-based microfluidics have evolved as a powerful platform to allow many chemical reactions within small volumes that each can be controlled and manipulated. A significant technical challenge is the ability to change the concentration of reactants inside a droplet. Here we describe a strategy that relies on the use of reactants that are soluble in both oil and water and allow a passive, diffusive exchange of reactants between the oil and aqueous phases to externally control composition of the droplets. We demonstrate the applicability of our approach by externally changing the pH inside microdroplets without the need for physical manipulation or droplet merging.