Drug treatment studies in laboratory mice typically employ manual administration methods such as injection or gavage, which can be time-consuming to perform over long periods and cause substantial stress in animals. These stress responses may mask or enhance treatment effects, increasing the risk of false positive or negative results and decreasing reliability. to address the lack of an automated method for drug treatment in group-housed mice, we have developed PiDose, a home-cage attached device that weighs individual animals and administers a daily dosage of drug solution based on each animal's bodyweight through their drinking water. Group housed mice are identified through the use of RFID tagging and receive both regular water and drug solution drops by licking at a spout within the PiDose module. This system allows animals to be treated over long periods (weeks to months) in a fully automated fashion, with high accuracy and minimal experimenter interaction. PiDose is low-cost and fully open-source and should prove useful for researchers in both translational and basic research. Biological research often involves treating experimental rodents with compounds over extended periods. A variety of routes of administration are used in these studies, with the goal to optimize delivery of the agent while reducing the potential for injury and procedure-associated stress. Parenteral administration via subcutaneous or intraperitoneal injection is often used due to the high bioavailability of injected drugs; however, repeated restraint and injection causes stress and puts the animal at risk of physical complications 1,2,3. These stress responses are particularly undesirable in behavioural studies, as chronic stress affects a variety of behaviours and may mask treatment affects and increase the risk of Type I/II errors 4,5. An alternative to injection is oral administration, which is often useful in a pre-clinical context as oral drug treatment is the most common and convenient route of administration in humans. Unfortunately, oral gavage presents the same problems as injection regarding treatment stress and the potential for injury 1,6. To avoid this, several studies have provided methods for the voluntary feeding of drugs to animals in a palatable form (e.g. sucrose water, peanut butter) 7,8,9,10. This avoids some of the side effects associated with injection and gavage, but is time-consuming for chronic experiments and involves extensive experimenter interaction, which in itself may be enough to increase animal stress 11. To circumvent the need for manual administration, other studies have mixed the drug with the animal's drinking water 12,13,14,15. However, this method typically estimates drug dosage based on the average bodyweight and water consumption for all mice in a cage. This relies on the assumption that mice are drinking an amount of water that is directly proportional to their bodyweight, for which there is not clear support. To avoid this caveat, animals can be single-housed, or double-housed with a divider....