Nerve growth is regulated by attractive and repulsive factors in the nervous system. Microscopic gradients of Collapsin-1/Semaphorin III/D (Sema III) and myelin-associated glycoprotein trigger repulsive turning responses by growth cones of cultured Xenopus spinal neurons; the repulsion can be converted to attraction by pharmacological activation of the guanosine 3＇,5＇-monophosphate (cGMP) and adenosine 3＇,5＇-monophosphate signaling pathways, respectively. Sema ill also causes the collapse of cultured rat sensory growth cones, which can be inhibited by activation of the cGMP pathway. Thus cyclic nucleotides can regulate growth cone behaviors and may be targets for designing treatments to alleviate the inhibition of nerve regeneration by repulsive factors.