The possible anti-stress activity of mulberry juice was investigated in mice. When mice were subjected to water immersion restraint stress at 25 degrees C for 8 h, the plasma lipid peroxide level, determined by the d-ROMs test performed 12 h thereafter, was almost doubled. After administration of mulberry juice one or two weeks before the stress loading, the lipid peroxidation was completely blocked. Administration of mulberry juice after the stress loading, without pre-administration, was also protective. ESR spectroscopy revealed that mulberry juice scavenged superoxide anion (generated by hypoxanthine and xanthine oxidase reaction), hydroxyl radical (produced by the Fenton reaction) and NO radical (generated by a NO donor) at approximately 50% efficiency of blueberry juice. Mulberry juice produced smaller amounts of radical at neutral to alkaline pH. The cytotoxic and anti-HIV activities of mulberry juice were 18% and >4-fold those of blueberry juice, respectively. These data suggest that the anti-stress activity of mulberry juice in vivo may be derived from its radical scavenging activity.