Neuronectin (NEC1) is a human extracellular matrix protein found throughout the white matter of rostral brain segments but not in most areas of the mesencephalon, in the pons, cerebellum, medulla, spinal cord, and peripheral nerves. This distribution may result from NEC1 expression by a unique subset of neural cells in the rostral brain or from expression by a more widely distributed cell type, conditional on induction of region-specific extrinsic factors. In this study, we show that two brain-derived polypeptides, acidic and basic fibroblast growth factor (FGF), induce NEC1 secretion in cultured neural cells. Induction is detected within five hours after addition of FGF, is reversible, and is blocked by inhibitors of RNA and protein synthesis. Other growth and differentiation factors do not induce NEC1, except for 12-O-tetradecanoyl phorbol-13-acetate, which acts through a different signalling pathway. Acidic and basic FGF may be members of a group of extrinsic factors that determine region-specific NEC1 expression in neural tissues.