The common occurrence of inconclusive results in blood donor screening for anti-Trypanosoma cruzi antibodies should be interpreted with caution. It is important to consider the fact that blood transfusion services in Brazil and some other Latin America countries simultaneously perform two tests that use different methodologies to detect anti-T. cruzi antibodies; this is determined by legislation currently in force in Brazil (Resolution 721 of August 9, 1989, and Resolution 1376 of November 19, 1993)(1-3). This issue of the Journal Brasileira de Hematologia e Hemoterapia includes a study from the Blood Bank in Uberaba that employed three tests: enzyme immunoassay (EIA), indirect hemagglutination and indirect immunofluorescence(4). Samples that presented discordantresults between tests were considered inconclusive, for example: positive in one or two tests and negative in the other(s) and for samples with optical density/cut-off limit (OD/CO) values of 0.8 to 1.2 (the gray zone) in the ELISA test. The high rates of inconclusive results reported are mostly a result of the sum of false results of the three tests. The diagnosis of Chagas disease is usually performed by the detection of anti-T. cruzi antibodies. Since Guerreiro and Machado developed the complement fixation method in 1913, the sensitivity and specificity of these tests have improved considerably(5). The first Brazilian legislation that mentioned serology screening for Chagas disease is a decree dated September 25, 1969, of the Comissao Nacional de Hemoterapia, that states in no 4, that serological screening for Chagas disease should be made prior to or subsequent to each donation and,when positive, the donor should be excluded and any collected blood discarded(6). The first generation of commercially available serological anti-T. cruzi tests employed purified or total antigenic fractions of the epimastigote form of T. cruzi with the high rate offalse positive as well as false negative results being unwanted characteristics of these tests. So,Decrees 721 of August 9, 1989 and 1376 of November 19, 1993 stipulate that serology screeningfor Chagas disease should be performed using two methods that apply different principles(1-3). With the advent of sequencing and cloning immunodominant antigens of T. cruzi came the development of tests using recombinant protein mixtures of the parasite and/or synthetic peptides which resulted in an increase in the sensitivity and specificity. Moreover, it was only with Resolution 343 of December 13, 2002, that highly sensitive blood donor screening for Chagas disease using an enzyme immunoassay (EIA) test was established as compulsory. At the same time, the blood transfusion services gradually implemented a set of quality control measures and introduced computer systems, which together, gradually reduced the number of erroneous and inconclusive results. In this study by Pereira et al.(4), the prevalence found in the group of inconclusive samples was 13.3%; Remesar et al.(7) reported a prevalence of 18% in Chaco province, Argentina, where the prevalence of the disease is high (24.5%), Otani et al.(8) found 17% in samplescollected from ten Latin America countries and Sabino et al. reported a prevalence of 20% for Brazil in the International Retrovirus Epidemiology Donor Study-II (REDS-II)(9). An understanding of the meaning of results with low reactivity in screening tests to detect anti- T. cruzi antibodies however has not been reached. Sabino et al. (in press) report that the drop in the S/CO index in ten patients with negative results for Chagas disease using a polymerase chain reactiontechnique may be an indication of seroreversion as a result of a spontaneous cure of the disease. The current work shows that the interpretation of the results of serology screening for anti- T. cruzi in association with the epidemiological data is strategically important for blood safety and for the diagnosis of Chagas disease(4).