An open system is provided for performing a submicroliter reaction. An open system can contain a solid support having a target site for performing the reaction; a liquid dispensing system such as a nanoliter dispensing pipette for dispensing a submicroliter amount of a liquid to the target site; a temperature controlling device for regulating the temperature of the support; and means for controlling the amount of liquid dispensed, which corresponds to the amount of liquid that evaporates from the target site. Also provided is an open system, including a solid support having a target site; a liquid dispensing system, which can dispense a liquid to the target site; a temperature controlling system, which regulates the temperature of the solid support; and an interface, which regulates an amount of liquid dispensed from the liquid dispensing system. Also provided is a method for performing a reaction in a submicroliter volume in an unsealed environment by dispensing a submicroliter volume of liquid onto the surface of a support; monitoring the temperature of the support; monitoring an amount or rate of evaporation of the liquid; and dispensing to the surface of the support a further amount of the liquid, which corresponds to the amount lost from the support due to evaporation, thereby maintaining the reaction volume at a predetermined volume throughout the course of the reaction. A method also is provided for maintaining a volume of a reaction mixture, which can be one of a plurality of reaction mixtures, on a solid support in an unsealed environment by monitoring the rate of evaporation of a liquid from the reaction mixture; and dispensing into the reaction mixture an amount of liquid that corresponds to the amount that evaporates.