Objective: To examine the effects of alpha(s1)-casein hydrolysate on females with stress-related symptoms. Design: Double-blind, randomized, crossover, placebo-controlled trial. Setting: The alpha(s1)-casein hydrolysate was manufactured by INGREDIA (Arras, France) and the placebo was manufactured by DIETAROMA (Bourg, France). Study was designed and performed at PROCLAIM (Rennes, France), and the statistical analyses were performed by D Desor (Nancy, France). Subjects: A total of 63 female volunteers suffering from at least one disorder that may be related to stress such as anxiety, sleep problems and general fatigue. Interventions: A total of 63 volunteers participated in a double-blind, randomized, crossover, placebo-controlled study. Subjects were randomly allocated to receive either tablets containing alpha(s1)-casein hydrolysate or placebo at the dose of 150 mg/day for 30 days. After a 3 weeks washout period, they were crossed over for a new 30-day period of tablets intake. The outcome measure was a questionnaire including 44 items of symptoms that may be related stress in which the severity of each sign was evaluated using a 10-degree scale. These measures were studied repeatedly at the day of 0, 15 and 30 after the start of each interventional period. Results: The 30-day treatment by alpha(s1)-casein hydrolysate in females with stress-related symptoms reduced their symptoms, particularly in digestion (P < 0.01), cardiovascular (P < 0.05), intellectual (P < 0.01), emotional (P < 0.05) and social problems (P < 0.05). Conclusion: This study showed that a 30-day ingestion of alpha(s1)-casein hydrolysate decreased the stress-related symptoms in females suggesting that this product may be used as an effective functional ingredient alleviating such symptoms. Sponsorship: This study was partially supported by the INGREDIA of France and Neurobiology Research Program from the Korea Ministry of Science and Technology (2004-01757) of Korea.