Capsule endoscopy for medical diagnosis in the gastrointestinal (GI) tract has emerged only in the past 10 years. Now established in "pillcams", which have benefitted more than 1 m patients worldwide, it is a clear candidate for further innovation. Most capsule endoscopy devices record and transmit video data representing the visual appearance of the inside of the gut, but work has begun on other diagnostic techniques, such as the measurement of pH, and there has been some research into the use of capsules for treatment as well. Medical ultrasound imaging is a safe, inexpensive technique which can be applied in real-time at the point of care. Ultrasound is also capable of treatment through focused ultrasound surgery and, in research, for targeted drug delivery. The core of the Sonopill programme is the exploration of ultrasound imaging and therapeutic capabilities deployed in capsule format. This will be supported by extensive pre-clinical work to demonstrate the complementary nature of ultrasound and visual imaging, along with studies of multimodal diagnosis and therapy, and of mechanisms to control the motion of the Sonopill as it travels through the GI tract. This brings research challenges and opportunities in areas including ultrasound device and systems design, microengineering and microelectronic packaging, autonomous capsule positioning, sensor suites for diagnosis and intervention, and routes to translation into clinical practice. Our carefully structured but open-ended approach maximises the possibility to meet these research challenges while delivering for the UK a sustainable international lead in multimodality capsule endoscopy, to provide greater capabilities for the clinician, more acceptable practice for the patient population, and lower costs for economic wellbeing.