A preparation of dissociated monolayer cultures from embryonic human spinal cord has been developed and characterized (Kato, Touzeau, Bertrand, Bader, 1985) as a model system for the study of amyotrophic lateral sclerosis (Touzeau and Kato, 1986). The cultures contain cholinergic and GABAergic neurons, astrocytes and fibroblasts. We have recently found that gamma-interferon (IFN) can increase the choline acetyltransferase (CAT) activity without altering the level of glutamic acid decarboxylase (GAD) or the neuronal survival; an antibody to IFN can prevent these effects. Gamma-IFN appears to mediate these effects via the non-neuronal cells since in the absence of non-neuronal cells, gamma-IFN has no effect on the cholinergic properties. The non-neuronal cells alone have no CAT or GAD activity. Astrocytes may be responsible for these changes since gamma-IFN increases the development of GFAP immunoreactivity in cultures of 6-7 week old spinal cord cells and it causes no visible change in the Thy-1 immunoreactivity of the fibroblasts. Thus we propose that IFN acts on non-neuronal cells, possibly the astrocytes, which in turn stimulate neuronal cholinergic traits either by means of a diffusible factor or via cell-cell contact. These studies could be relevant in understanding the effects of the immune system on the nervous system and also in the search for new drugs which act specifically on cholinergic neurons.