Neuraminidase was injected into the cerebrospinal fluid of normal rats to investigate the assembly and fate of the desialylated Reissner’s fiber glycoproteins. It was established that a single injection of neuraminidase cleaved the sialic acid residues of the Reissner’s fiber glycoproteins that had been assembled before the injection, and of the molecules that were released over a period of at least 4 h after the injection. These desialylated glycoproteins underwent an abnormal assembly that led to the formation of spheres instead of a fiber. The number of these spheres increased during the 4-h period following the injection, indicating that neuraminidase did not prevent the secretion of the Reissner’s fiber glycoproteins into the cerebrospinal fluid. The spheres remained attached to the surface of the subcommissural organ and became intermingled with infiltrating cells, many of which were immunocytochemically identified as macrophages. The latter were seen to contain immunoreactive Reissner’s fiber material. It is concluded that the desialylated Reissner’s fiber glycoproteins forming the spheres underwent an in situ degradation by macrophages, thus resembling the normal process undergone by the Reissner’s fiber glycoproteins reaching the massa caudalis.