A possible relationship between human circadian rhythmicity and polymorphisms in clock genes have been documented. However, these data are controversial, and studies both corroborating and denying them have been reported. T3111C Clock polymorphism had been associated with the human evening preference, however, this association has not been confirmed. Moreover, C111G Per2 polymorphism has been associated with the "morning larks" chronotype in one study, not yet replicated. We have, therefore, performed this study to evaluate whether Per2 C111G and Clock T3111C polymorphisms might influence sleep circadian rhythmicity in a sample of 219 Italian volunteers. A possible interaction between these polymorphisms was also investigated. No differences in Per2 C111G and Clock T3111C allele and genotype frequencies were found, and none of the combined Clock T3111C-Per2 C11G genotypes resulted more frequent in one group compared to the others. Present results do not support a role of these polymorphisms in the circadian phenotypes.