Recent studies have suggested a role of two polymorphisms of the dopamine D4 receptor gene (DRD4 exon III and –521C/T) in the modulation of personality traits such as ‘novelty seeking’ or ‘extraversion’, which are supposed to be modulated by individual differences in dopaminergic function. However, several replication studies have not provided positive findings. The present study was performed to further investigate whether DRD4 exon III and –521C/T are associated with individual differences in personality. One hundred and fifteen healthy German volunteers completed the NEO-Five-Factor Inventory (NEO-FFI) and were genotyped for the two DRD4 polymorphisms. We found no association between DRD4exon III and –521C/T, respectively, and estimated novelty seeking, NEO-FFI extraversion or other personality factors. Our findings are in line with several earlier studies which have failed to replicate the initial association results. Hence, our data do not provide evidence for a role of DRD4 exon III and the –521C/T polymorphism in the modulation of novelty seeking and extraversion.