Perlecan is a highly conserved heparan sulfate proteoglycan in cartilage and basement membranes. We identified chick perlecan and a 90 KD perlecan fragment in vivo using a newly generated monoclonal antibody. Chick perlecan is, like its human and mouse homologue, a hybrid heparan sulfate/chondroitin sulfate proteoglycan with a core protein of 400 KD. Analysis of the 90 KD fragment by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and Capillary LC nano Electrospray Ionization tandem MS (LC nano ESI MS/MS) showed that it belonged to domain IV of the perlecan core protein. We found that full-length perlecan and its domain IV fragment are abundant in embryonic vitreous body and serum. Their expression in vitreous and serum is greatly down-regulated shortly after hatching of the chick. We speculate that the abundance of perlecan in the embryonic circulation and vitreous reflects the ongoing formation of new BMs in the expanding vascular system and the growing retina. In addition, we found that perlecan as a substrate does not support, rather inhibits neurite outgrowth.