This is the first of three papers describing new components and structural relationships within the neuronal endomembrane system. This system includes: the nuclear envelope, rough endoplasmic reticulum, the Golgi apparatus, lysosomes, axoplasmic reticulum, and discrete cytoplasmic compartments such as vesicles, multivesicular bodies, and so on. Previous high voltage electron microscope studies of osmium-impregnated Golgi apparatus have shown that small varicose tubules often arise from the cis element. In bullfrog spinal ganglia, these tubules have been seen to extend into cytoplasmic domains occupied by rough endoplasmic reticulum (RER). This study was undertaken to determine whether varicose tubules form direct connections with RER and to measure cytoplasmic density of varicose tubules. Spinal ganglia from Rana catesbeiana were fixed by osmium impregnation and, in some cases, were then stained en bloc with lead aspartate. Sixty- to 3000-nm-thick sections of this tissue, as well as of ganglia prepared by conventional protocol, were studied using standard and high voltage electron microscopy. Quantitative analysis revealed that 9% of the varicose tubules connected with the Golgi cis element. To determine whether continuities existed between RER and any of these tubules, more than 50 tubules were fully reconstructed from images of serial sections. The "ends" of these reconstructed tubules were then studied by high magnification stereoscopy. This was facilitated by the en bloc lead staining which allowed visualization of unimpregnated RER elements along with the impregnated tubules. Small varicose tubules as well as larger smooth tubules were found to have formed confluent bridges between the cis element and RER. In addition, the varicose tubules were found to bridge widely separated elements of RER. Finally, numerous examples of varicose and smooth tubules were seen to extend from RER and from cis elements to eventually form blind endings. These findings raise the possibility that the tubules form highly dynamic transitory connections between RER and the Golgi apparatus as well as between separated elements of RER. Those between RER and Golgi apparatus are ideally positioned to play a major role in the transfer of protein or lipid components first assembled in RER to the Golgi apparatus for terminal synthetic modification.