The retrograde axoplasmic transport of foreign proteins in the rat visual system shows certain specificities. The molecular features of these proteins which may underlie their entry into the retrograde phase have been examined using biochemical and morphologic techniques. Of the isoenzymes of horseradish peroxidase (HRP), the basic isoenzyme C is strongly transported, while the acidic isoenzymes Abeta and Aalpha are transported weakly and not at all, respectively. Decreasing the isoelectric point (pI) of isoenzyme C from 8.2 to 4.4 decreases its transport, but a basic pI is not the sole requisite for transportability since two other basic peroxidases (turnip isoenzyme P7 and lactoperoxidase) are not transported in retrograde. The sugar component as a whole of isoenzyme C does not appear to be required for determining transport. Isoenzyme C and the other proteins which are transported enter multivesicular bodies in axons and axon terminals, as well as synaptic and coated vesicles and fine tubules in axon terminals. The non-transported proteins enter only the vesicular organelles thought to be involved in neurotransmitter recycling in axon terminals and do not enter multivesicular bodies. Thus the two systems of axonal membraneous compartments involved in local synaptic recycling versus the retrograde phase of transport do not show the same specificity of uptake of extracellular tracers and can be dissociated by the experimental use of these peroxidases.