Our aim was to investigate the long term effectiveness of intravenous immunoglobulin (IVIG) against intractable childhood epilepsy in the era of new antiepileptics and to determine the predictors of a favorable response in a prospective open-label add-on study. Of thirty-seven 9.9+/-0.9-year-old patients (11 with partial seizures, 26 with generalized seizures of whom 9 had West syndrome and 17 Lennox-Gastaut syndrome) followed for 15+/-3 months, 43% had a >50% decrease in seizures (including 15% seizure free, 229+/-58 compared with 104+/-3 seizures/month, P=0.035: generalized 246+/-318 to 117+/-200, P=0.025, partial 191+/-437 to 72+/-179, P>0.05; power=0.2). Males were more likely to respond than females (P=0.011, odds ratio=9.3). Review of the literature revealed nine other articles reporting efficacy of IVIG against epileptic seizures. Only one other used statistical methods and, unlike ours, showed only a trend toward seizure frequency reduction without achieving statistical significance, presumably because it was underpowered. These results indicate large-scale controlled studies of IVIG in epilepsy are still needed.