A comparison between genome size and some phenotypic parameters, such as developmental length and metabolic rate, showed in reptiles a nucleotypic correlation similar to the one observed in birds and mammals. Indeed, like homeotherms, reptiles exhibit a highly significant, inverse correlation of genome size with metabolic rate but unlike amphibians, no relationship with developmental length. Several lines of evidence suggest that these nucleotypic correlations are influenced by body temperature, which also affects the guanine + cytosine nuclear percentage, and that they play an important role in the adaptation of these amniotes. However, the reptilian suborders exhibit differences in the quantitative and compositional characters of the genome that do not completely correspond to differences in the phenotypic parameters commonly involved in the nucleotypic effect. Thus, additional factors could have influenced genome size in this class. These data could be explained with the model of Hartl and Petrov, who observed an inverse correlation between genome size, non-coding portion of the genome and rate of DNA loss and hypothesized a strong role for different spectra of spontaneous insertions and deletions (indels) in the variations of genome size. It is thus reasonable to surmise that variations in the reptilian genome were initially influenced by different indels spectra typical of the diverse lineages, possibly related to different chromosome compartmentalizations. The consequent size increases or decreases would have influenced various morphological and functional cell parameters, and through these some phenotypic characteristics of the whole organism, especially the metabolic rate, very important for environmental adaptation and thus subject to natural selection. Through this “nucleotypic” bond, natural selection would also have controlled genome size variations.