Embryonic rat brainstem slices including the facial and hypoglossal motor nuclei were maintained in organotypic cocultures with explants of embryonic tongue or post-natal skeletal muscle for periods up to 3 weeks. Survival and differentiation of motoneurones were dependent both on the type of muscle explant and its position relative to the brainstem. Tongue explants induced a more important glial outgrowth, a motoneurone migration towards the muscle, earlier muscular contractions and a more complete neuronal and muscular differentiation. Since the foetal tongue contains IGF levels as high as foetal liver, these effects might be due in part to diffusion of IGF from the explanted muscle. Indeed, foetal liver explants or crude foetal liver extracts induced effects similar to those of tongue explants. These effects can be reproduced by addition of IGF-1 or IGF-2, or both, into the culture medium. Although IGF-1 and IGF-2 had similar effects, IGF-1 induced a more pronounced muscular differentiation and IGF-2 promoted neuronal differentiation. Our results suggest that IGFs are good candidates as muscle-derived neurotrophic factors promoting survival and differentiation of rat cranial motoneurones. These results also stress the importance of neuroglial trophic interactions and target development.