Human recombinant interleukin-6 (IL-6, B-cell stimulating factor-2) was capable of supporting neuronal survival in cholinergic neuron culture, prepared from 10-day-old rat brain septal region. Cell survival of the cultured cholinergic neurons was estimated by measuring the remaining choline acetyltransferase (ChAT) activities after 6 days of culture. IL-6 at a concentration of 5 ng/ml maintained a more than 3-fold higher ChAT activity in the culture as compared with that in cultures without IL-6. The maximal dose of IL-6 was near 50 ng/ml. The concomitant addition of mouse nerve growth factor (NGF) and IL-6, both at maximal doses, had a synergistic effect on cholinergic cell survival. These results indicate that IL-6 can act as a neurotrophic agent, independent of the action of NGF, supporting neuronal survival of cultured postnatal rat septal cholinergic neurons. On the other hand, IL-6 did not affect the differentiation of the cultured embryonic rat septal cholinergic neurons, differently from the differentiation action by NGF.