Selective destruction of neurons based on the use of targeted toxins has proven successful for several types of neurons (1). This chapter will describe the use of an immunotoxin to selectively destroy rat neurons that express the low-affinity neurotrophin receptor (p75NTR) (2). This immunotoxin consists of a monoclonal antibody disulfide coupled to a ribosome inactivating protein. The most extensively used and studied version uses the antibody 192 IgG originally developed as an antibody to a rat NGF-binding protein (3). 192 IgG has been extensively used to study rat p75NTR. Results of these studies have demonstrated p75NTR expression on a variety of neurotrophin-responsive cells, including sympathetic ganglion neurons, some primary sensory neurons, and cholinergic neurons of the basal forebrain. p75NTR also is expressed on cells not known to be responsive to neurotrophins, such as cerebellar Purkinje neurons and numerous other tissues during development (4). Thus, producing selective lesions using 192 IgG also requires restricting application of the immunotoxin to the region of the target cells.