Although the current risk of posttransfusion infection is very low in North America and Western Europe, there continues to be considerable interest in measures to inactivate residual viruses in blood components. The human immunodeficiency virus is of greatest concern, but hepatitis C virus is also considered to be a significant problem. HTLV-I and -II and HBV may also be transmitted by transfusion, although infrequently. It is likely that effective inactivation methods will have to reduce viral titers by about 6 orders of magnitude, including both viruses found free in plasma and those in intracellular compartments. Although it would be most desirable to have a single procedure to inactivate viruses in all blood components, it appears that different methods may be required for plasma, red cells and platelets. To date, the most promising approach for platelets appears to be photochemical inactivation. In general, photoactive compounds fall into two major groups: photodynamic dyes which are activated by visible light and act by oxygen dependent generation of reactive molecular species; and ultraviolet-activated intercalating compounds which form covalent adducts with nucleic acids. We have found that photodynamic inactivators are unable to inactivate viruses in platelet concentrates without damaging the platelets. On the other hand, we have shown that aminomethyl trimethyl psoralen (AMT), when activated by long-wavelength ultraviolet light (UVA) can inactivate more than 5 logs of model viruses and HIV while platelet in vitro properties are maintained. Further, unlike photodynamic inactivators, AMT is able to inactivate cell-associated and intracellular viruses and also prevents the replication of integrated HIV genome sequences, as demonstrated by PCR.(ABSTRACT TRUNCATED AT 250 WORDS)