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The occurrence of mutual genetic loci in morphogenesis of the face and teeth implies shape covariation between these structures. However, teeth finalize their shape at an early age, whereas the face grows and is subjected to environmental influences for a prolonged period; it is therefore conceivable that covariation might modulate with age. Here we investigate the extent of this covariation in humans by measuring the 3D shape of the occlusal surface of the permanent first molars and the shape of the craniofacial complex from lateral radiographs, at two maturations stages. A sample of Greek subjects was divided into two groups (110 adult, 110 prepubertal) with equally distributed gender. The occlusal surfaces of the right first molars were 3D scanned from dental casts; 265 and 274 landmarks (including surface and curve semilandmarks) were digitized on the maxillary and mandibular molars, respectively. The corresponding lateral cephalometric radiographs were digitized with 71 landmarks. Geometric morphometric methods were used to assess shape variation and covariation. The vertical dimension of the craniofacial complex was the main parameter of shape variation, followed by anteroposterior deviations. The male craniofacial complex was larger (4.0-5.7%) and was characterized by a prominent chin and clockwise rotation of the cranial base (adult group only). Allometry was weak and statistically significant only when examined for the sample as a whole (percent variance explained: 2.1%, P = 0.0002). Covariation was statistically significant only between the lower first molar and the craniofacial complex (RV = 14.05%, P = 0.0099, and RV = 12.31%, P = 0.0162, for the prepubertal and adult groups, respectively). Subtle age-related covariation differences were noted, indicating that environmental factors may influence the pattern and strength of covariation. However, the main pattern was similar in both groups: a class III skeletal pattern (relative maxillary retrusion and mandibular protrusion), hyperdivergency, forward rotation of the posterior cranial base and upward rotation of the anterior cranial base were associated with mesiodistal elongation of the lower molars and height reduction of their distal cusps. This pattern mimics phylogeny in humans, where flexion and counterclockwise rotation of the cranial base, considered advantageous to survival, co-occur with tooth reductions that cannot be easily explained in evolutionary terms. The similarity of the phylogenetic and covariation patterns seems to support the pleiotropic gene hypothesis., (© 2014 Anatomical Society.)