This study examines the potential efficacy of acetyl-l-carnitine (ALC) to prevent and treat paclitaxel-induced pain. Rats received four intraperitoneal (i.p.) injections of 2 mg/kg paclitaxel on alternate days which, following a short delay induced marked mechanical hypersensitivity. Daily administration of ALC (50 mg/kg and 100 mg/kg; p.o.; concurrently with paclitaxel and for 14 days afterwards) prevented the development of paclitaxel-induced pain. This effect was long lasting, for at least 3 weeks after the last dose of ALC. In a separate experiment, daily administration of ALC (100 mg/kg; p.o.; for 10 days) to rats with established paclitaxel-induced pain produced an analgesic effect. This effect dissipated shortly after ALC treatment was withdrawn. We conclude that ALC may be useful in the prevention and treatment of chemotherapy-induced painful peripheral neuropathy.