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Having a good “sense of humor” is an important personality characteristic that significantly influences social communication and may represent an important coping strategy. To take things “with humor” does not only represent a state characteristic but also a personality trait that can reliably be assessed with questionnaires like the “state–trait–cheerfulness–inventory” (STCI) by Ruch [Ruch et al., Assessing the “humorous temperament”: construction of the facet and standard trait forms of the state–trait–cheerfulness–inventory—STCI, Humor 9 (1996) 303–339]. Substantial inter-individual differences among study subjects are a key feature of almost all functional magnetic resonance imaging studies on higher cognitive functions. Usually, they are considered as “statistical noise” and are not recommended for the data analysis, although they can have a high intra-individual stability. However, a number of recent fMRI studies found robust correlations between inter-individual differences in BOLD response and personality traits such as extraversion. The aim of this pilot exploratory study was to localise regions where the BOLD response was predicted by “humor personality” scores. 10 healthy male subjects viewed funny or non-funny versions of Gary Larson cartoons while BOLD response was measured with functional magnetic resonance imaging (fMRI). Data were collected from the whole brain (28 slices, slice thickness 4 mm, 1 mm gap, TR = 3 s). SPM 99 software was used. A simple regression analysis with the sub-score cheerfulness from the STCI was applied. Higher cheerfulness in the STCI predicted brain activation in the right inferior parietal lobule (Tal X, Y, Z: 45, −77, 29), but not in limbic and prefrontal brain areas. We conclude that neural correlates of cheerfulness are correlated with BOLD response in lateral cortical rather than limbic brain areas. Likely the activated region is important for a readiness or tendency to be amused, whereas the regions previously shown to be activated in humor appreciation studies are related to the understanding of the joke and the emotional reaction.