A key trend in high-throughput screening is assay miniaturization to control reagent costs and increase throughput. For this purpose, liquid-handling devices are used that transfer nano-to low-microliter volumes into all currently used microtiter well plates. One drawback of many available dispenser and pipetting systems are high dead volumes. Therefore, the authors were looking for an easy and simple solution to modify their standard liquid-handling device, PerkinElmer’s FlexDrop™ Precision IV, allowing for a dead volume reduction to receive maximum benefit from miniaturized assay formats. Internal reservoirs were developed and constructed by Schering’s Technical Development Laboratory (TDL), which are directly connected to the dispenser banks of FlexDrop™ without tubing. Using these newly built reservoirs, the dead volume was decreased by a factor of 5 in comparison to the manufacturer’s reservoirs without compromising liquid-handling parameters such as accuracy and precision. The modified system displayed a high robustness and reliability under routine high-throughput screening conditions.