Humour occupies a special place in human social interactions. The brain regions and the potential psychological processes underlying humour appreciation were investigated by testing patients who had focal damage in various areas of the brain. A specific brain region, the right frontal lobe, most disrupted the ability to appreciate humour. The individuals with damage in this brain region also reacted less, with diminished physical or emotional responses (laughter, smiling). Performance on the humour appreciation tests used were correlated in a distinct pattern with tests assessing cognitive processes. The ability to hold information in mind (working memory) was related to both verbal (jokes) and non-verbal (cartoon) tests of humour appreciation. In addition, the demands of the specific type of humour test were related in a logical manner to cognitive processes, verbal humour being associated with verbal abstraction ability and mental shifting and cartoon humour being related to the abilities to focus attention to details and to visually search the environment. The ability of the right frontal lobe may be unique in integrating cognitive and affective information, an integration relevant for other complex human abilities, such as episodic memory and self-awareness.