BACKGROUND: This study evaluated the efficacy of photochemical treatment (PCT) with amotosalen and ultraviolet A (UVA) light to inactivate Trypanosoma cruzi in contaminated platelet (PLT) components. STUDY DESIGN AND METHODS: Fifteen pools of buffy-coat PLTs (BC-PLTs) were inoculated with approximately 5 x 10(3) to 5 x 10(5) per mL of viable T cruzi of the G, Tulahuen (T), or Y strains. Samples from BC-PLTs were assayed for infectivity before and after PCT with 150 mu mol per L amotosalen and 3 J per cm(2) UVA light. Infectivity was determined with three different methods: 1) in vitro culture to detect viable epimastigotes, 2) [3 H]thymidine incorporation in culture, and 3) in vivo inoculation into interferon-gamma receptor (IFN-gamma R)-deficient mice. RESULTS: The in vitro assay yielded viable parasite titers of 3.9 x 10(5), 2.8 x 10(4), and 5.6 x 10(3) per mL (corresponding to 5.6, 4.4, and 3.8 logs/mL) for the Y, T, and G strains, respectively. PCT was able to inactivate all three strains of T cruzi to below the limit of detection (10 parasites/mL) in the sensitive in vivo assay. Because 10-mL samples, each concentrated into a 1-mL sample for inoculation, were tested in the in vivo assay, log reductions achieved were greater than 5.6, greater than 4.4, and greater than 3.8 for the Y, T, and G strains of T cruzi, respectively. CONCLUSIONS: The pathogen reduction system with amotosalen HCl and UVA demonstrated robust efficacy for inactivation of high doses of three different strains of T cruzi and offers the potential to Make the PLT supply safer.