Publisher Summary This chapter discusses the phenomena of axonal sprouting from mature neurons in vivo and in organ culture. Within hours of injury to a nerve, axonal sprouts form at the proximal stump. These sprouts are the initial stage of the regenerative process and have many of the characteristics of the growth cones of neurites formed from neuronal cells in tissue culture. The axonal sprouts formed from a nerve-ganglion preparation in organ culture are, initially at least, indistinguishable from their in vivo counterparts and provide a method for studying axonal sprouting under controlled conditions. In particular, the nerve-ganglion preparation allows studying the factors that initiate sprouting. Blockade by colchicine suggests that axonal transport is necessary for axonal sprouting, but it is uncertain whether the initial stimulus for sprouting is intraneuronal or a response to an exogenous factor, such as a product of tissue damage. Collateral reactive sprouting and regenerative sprouting may share a common stimulus.