The potential risk of acquiring a transfusion-transmitted infection by the human immunodeficiency virus (HIV), hepatitis B (HBV) virus, hepatitis C (HCV) virus, or Trypanosoma cruzi was estimated for seven South American and five Central American countries during the period 1994-1997. The estimates were based on official national reports of the number of donors, blood screening coverage, and prevalence of serologic markers for infectious diseases. Coverage of screening in 1997 was 100% in 12 and 11 countries for HIV and HBV respectively. Complete screening for HCV was reported by only one country in 1994 and by six in 1997. For T. cruzi, the number of countries with 100% screening coverage increased from two in 1994 to four in 1997. In 1994, three countries showed risk of transfusion-transmitted infections for HIV, seven for HBV, eight for HCV, and seven for T. cruzi. The risk of receiving an infected blood unit and acquiring a transfusion-transmitted infection has been reduced with time in 10 of the 12 countries due to improvements in screening coverage. In Uruguay, the risk was theoretically nil from 1994-1997 because at the beginning of the study period they already had 100% blood donor screening for all infectious diseases transmitted by blood. In 1994, Colombia and Venezuela had the highest health risk associated with blood transfusion (spreading index of 101 and 62, respectively); during the period 1996-1997, Costa Rica presented the highest figures (spreading index of 53 and 83, respectively). The analysis of the potential risk associated with transfusion of tainted blood highlights the need for continuous monitoring of the safety of blood supply.