Motivation: In the biological sciences, the need to analyse vast amounts of information has become commonplace. Such large-scale analyses often involve drawing together data from a variety of different databases, held remotely on the internet or locally on in-house servers. Supporting these tasks are ad hoc collections of data-manipulation tools, scripting languages and visualisation software, which are often combined in arcane ways to create cumbersome systems that have been customised for a particular purpose, and are consequently not readily adaptable to other uses. For many day-to-day bioinformatics tasks, the sizes of current databases, and the scale of the analyses necessary, now demand increasing levels of automation; nevertheless, the unique experience and intuition of human researchers is still required to interpret the end results in any meaningful biological way. Putting humans in the loop requires tools to support real-time interaction with these vast and complex data-sets. Numerous tools do exist for this purpose, but many do not have optimal interfaces, most are effectively isolated from other tools and databases owing to incompatible data formats, and many have limited real-time performance when applied to realistically large data-sets: much of the user's cognitive capacity is therefore focused on controlling the software and manipulating esoteric file formats rather than on performing the research. Methods: To confront these issues, harnessing expertise in human-computer interaction (HCI), high-performance rendering and distributed systems, and guided by bioinformaticians and end-user biologists, we are building reusable software components that, together, create a toolkit that is both architecturally sound from a computing point of view, and addresses both user and developer requirements. Key to the system's usability is its direct exploitation of semantics, which, crucially, gives individual components knowledge of their own functionality and allows them to interoperate seamlessly, removing many of the existing barriers and bottlenecks from standard bioinformatics tasks. Results: The toolkit, named Utopia, is freely available from http://utopia.cs.man.ac.uk/. © 2009 Pettifer et al; licensee BioMed Central Ltd.