Development of the nervous system depends on the correct pathfinding and target recognition by the growing tip of an axon, the growth cone. Diffusible or substrate-bound molecules present in the environment may serve as either attractants or repellents to influence the direction of growth-cone extension. Here we report that differences in cyclic-AMP-dependent activity in a neuron may result in opposite turning of the growth cone in response to the same guidance cue. A gradient of brain-derived neurotrophic factor normally triggers an attractive turning response of the growth cone of Xenopus spinal neurons in culture, but the same gradient induces repulsive turning of these growth cones in the presence of a competitive analogue of cAMP or of a specific inhibitor of protein kinase A. This cAMP-dependent switch of the turning response was also found for turning induced by acetylcholine, but not for the turning induced by neurotrophin-3 (NT-3). Thus, in the presence of other factors that modulate neuronal cAMP-dependent activity, the same guidance cue may trigger opposite turning behaviours of the growth cone during its pathfinding in the nervous system.