Since HIV first burst onto the scene of transfusion medicine, the quest for viral inactivation processes for plasma and plasma products has not ceased. Sophisticated methods for improving viral safety are currently used in the industrial world. However, in developing countries, with no facilities for treating plasma, nonviral-inactivated fresh frozen plasma [FFP] continues to be used extensively, and as screening may not be optimal (or may even be absent), FFP still contributes to the spread of HIV and other infectious viruses. The feasibility of heat-treating FFP at the liquid state, in its collection bag, was explored by testing diverse conditions of temperature and duration, in the presence of biologically compatible stabilisers. Quality of the heat-treated plasma was evaluated by haematological, biochemical and animal assays. The efficiency of the method to inactivate viruses was validated using HIV and model viruses. The selected heating conditions are 50 degrees C for 3 h. The optimized combination of stabilizers is composed of 30 mM trisodium citrate, 10 g L-1 L-lysine, 12 mM calcium gluconate and 150 g L-1 sorbitol. Plasma coagulability is appropriately preserved as shown by the KCT ratio (1.4). Recovery of biological activity of most coagulation factors is higher than 70% (including fibrinogen & von Willebrand factor). Electrophoretic and immunoblotting studies did not evidence protein aggregation and/or degradation. Viral validation studies of this procedure have shown complete inactivation of HIV (> 6.6 log) in less than 1 h of treatment. A viral reduction of at least 4 log for various model viruses, including those of hepatitis A and C viruses, suggests a potential contribution of the method to diminish the risk from various blood-borne viruses. The selected formulation appears to preserve plasma protein integrity and properties. The procedure does not require sophisticated equipment but it is mandatory to monitor it carefully to ensure quality and reproducibility. If properly controlled and standardized, this approach offers an opportunity to reduce the risk of transmission of HIV and other viruses, particularly in poor countries with a high incidence of HIV.