Purpose: A 2 and A 2 B are rare phenotypes of the ABO blood group system. Some individuals with A 2 and A 2 B may have anti-A 1 antibodies that may be clinically significant or insignificant. The aim of this study was to determine the frequency of A 2 , A 2 B phenotypes and anti-A 1 antibodies in blood donors in Jazan, Saudi Arabia. This study also evaluated the reactivity potential of anti-A 1 antibodies. Materials and Methods: Blood samples collected from 446 blood donors were typed for ABO (cell and serum grouping) and Rh D. Individuals with blood group A and AB were further subtyped by testing with anti-A 1 lectin. In addition to the serum grouping using A 1 red cells, A 2 and A 2 B individuals were screened for the presence of anti-A 1 in their sera against A 1 red cells at 4°C, 22°C and 37°C to determine the thermal amplitude of the reacting anti-A 1 antibody (if present). Results: Among A and AB, A 1 was the commonest phenotype (20.2%, n=90 out of 446) while A 1 B was found to be 1.8% (n=8) among AB phenotype. A 2 and A 2 B were found to be 2.2% (n=10) and 0.9% (n=4), respectively. Only one individual with A 2 B blood type showed cold reactive anti-A 1 antibody, the strength of which was 32. Conclusion: A 2 and A 2 B were the rarest among ABO phenotypes in the studied population. Although rare, anti-A 1 antibody is not so uncommon. Care shall be taken during routine ABO grouping especially in cases of mix-field or weak positive reactions in A and AB phenotypes.