We have studied the effects of tissue transplants and antibodies (IN-1) against the myelin-associated neurite growth inhibitory proteins on sprouting and regeneration of the rat corticospinal tract (CST). Transplantation of embryonic spinal cord tissue into bilateral transection lesions of the lower thoracic spinal cord in young adult rats resulted in a marked increase of the sprouting of the lesioned CST. This sprouting effect was probably elicited by soluble factors released from the transplants, and was enhanced by the IN-1 antibodies. The retraction of lesioned CST fibres normally observed with prolonged survival times was also reduced by the presence of transplants. In spite of these growth-promoting effects of the transplants, the regenerative elongation of CST sprouts into the caudal spinal cord was dependent upon the neutralization of the myelin-associated inhibitory proteins. In the controls (no antibodies or control antibodies) only 27% of the animals showed elongation of CST fibres exceeding the sprouting distance of 0.7 mm. These fibres grew to a maximal length of 1.8 mm (mean +/- SEM, 1.2 +/- 0.1). In contrast, 60% of the IN-1-treated, transplant-containing rats showed elongations of > 0.7 mm, and these fibres grew up to 10.1 mm (4.6 +/- 0.5). Regenerating fibres crossed the lesion site through remaining tissue bridges. Neither embryonic spinal cord transplants nor a variety of implanted bridge materials could serve as a substrate for the regenerating CST axons.