The role of red cell antigens is determined by biological antibody responses to systemic antigens. ABO-isohemagglutinins (IH) are part of the ABO blood group system, playing a major role in the outcome of transfusion therapy and organ transplantation. The presence of ABH-antigens on the cells of different origin determines their role in the graft versus host reaction, whereas in blood transfusion they are involved in the undesired donor-recipient reaction. IH are diversified by specificity, immunoglobulin classes and variable serum levels, which has been associated with demographic characteristics and ethnographic origin that is indirectly influenced by the environment, exposure to microorganisms, allergens, dietary habits and vaccination. Considering their unclear etiology, it has been postulated that the formation of IH is stimulated by the exposure to ubiquitous antigens due to compatibility with blood group antigens. In this study is determinated the level and presence of IH classes in the blood of healthy Croatian population and assesed the impact of ABO antigen status, age, sex and season on IH level modification. The immunoenzymatic method was used to determine direct relationship of IH immunoreactions to common respiratory allergens as a possible consequence of cross-reactivity.