A photochemical treatment process has been developed for the inactivation of viruses and bacteria in platelet concentrates. This process is based on the photochemical reaction of a novel psoralen, S‐ 59, with nucleic acids upon illumination with long‐wavelength ultraviolet light (UVA, 320–400 nm). High levels of pathogens were added to single‐donor platelet concentrates containing 3 to 5 × 10(11) platelets in 300 mL of 35‐percent autologous plasma and 65‐percent platelet additive solution. After treatment with S‐59 (150 microM) and UVA (0–3 J/cm2), the infectivity of each pathogen was measured with established biologic assays. In vitro platelet function after photochemical treatment was evaluated during 7 days of storage by using a panel of 14 assays. The in vivo recovery and life span of photochemically treated platelets were evaluated after 24 hours of storage in a primate transfusion model. The following levels of pathogen inactivation were achieved:>10(6.7) plaque‐forming units (PFU) per mL of cell‐free human immunodeficiency virus (HIV),>10(6.6) PFU per mL of cell‐associated HIV,>10(6.8) infectious dose (ID50) per mL of duck hepatitis B virus (a model for hepatitis B virus),>10(6.5) PFU per mL of bovine viral diarrhea virus (a model for hepatitis C virus),>10(6.6) colony‐forming units of Staphylococcus epidermidis, and>10(5.6) colony‐forming units of Klebsiella pneumoniae. Expression of integrated HIV was inhibited by 0.1 microM S‐ 59 and 1 J per cm2 of UVA. In vitro and in vivo platelet function were adequately maintained after antiviral and antibacterial treatment. Photochemical treatment of platelet concentrates offers the potential for reducing transfusion‐related viral and bacterial diseases.