Sodium phenylbutyrate (NaPB) is used in urea cycle disorders. We screened 6 neuroblastoma cell lines for in vitro potency of NaPB as an antiproliferative agent, evaluated multiple dosing schedules, and assessed its activity in combination with clinically active agents for neuroblastoma. We determined that NaPB achieves a 30-80% growth inhibition at 5 mM. Repeated dosing and prolonged drug exposure enhanced the cytotoxic effect. NaPB had additive cytotoxic effects when administered with vincristine; however, NaPB did not affect the activity of etoposide, adriamycin, 4-hydroxycyclophosphamide or cisplatinum. These results suggest that NaPB is an active agent against neuroblastoma and could be combined with vincristine in novel chemotherapy regimens.