The search for understanding the population dynamics of genes and blood group genotypes in the ABO / Rh system is an important field of Population Genetics. Thus, this study aimed to identify genetic variability; phenotypic, allelic and genotypic frequencies of the ABO and Rh blood group systems and compare de number of blood donations performed in the south Brazil region. In order to determine and analyze the occurrence of the main phenotypic, genotypic and allele classes related to the ABO / Rh blood system, data collection was performed, referring to 64,066 blood donors who donated during the period from over 10 years. The population genetic profile analysis was performed based on the principles of Hardy-Weinberg equilibrium theorem the distribution of ABO blood group system observed was: O> A> B> AB. O represents 50.15% of donors, A represents 36, 11%, B represents 10.14% and AB only 3.58%. The phenotypic frequency for each one of these groups is: O = 0.5015, A = 0.3611, B = 0.1014 and AB = 0.0358. Regarding genotypic frequency, the homozygous genotype (ii) for type O prevailed, with 0.5016 (50.16%). For blood types A and B, heterozygous genotypes are more frequent, I^A i and I^Bi frequencies were 0.1582 (15.82%) and 0.0503 (5.03%), respectively. A and B Homozygotes have a reduced frequency, with I^A I^A 0.0499 (4.99%) and I^B I^B 0.0051 (0.51%). The genotype for type AB (I^A I^B) has the frequency 0.0158 (1.25%). Among donors, Rh positive blood type predominated with a total of 55,551 people, with a phenotypic frequency of 0.8670 (86.70%), while Rh negative blood group was present in 8,515 donors only, with a phenotypic frequency of 0,1329 (13.29%). The analysis of interaction between the two studied blood group systems (ABO and Rh) made possible to verify the percentage of each type of heterozygote present in the data. In this way, 68% were I^Ai/Dd, 21.6% were I^Bi/Dd. and 6.86% were I^AI^B/Dd. These data analyses together are helpful in understanding the differentiation of blood group loci and for designing prospective studies for establishing the associations of these loci with health variables in the populations studied.