Major reorganization in the central nervous system (CNS) takes place during metamorphosis in holometabolan insects (G. Technau and M. Heisenberg, 1982, Nature (London) 295, 405-407. J. W. Truman and S. E. Reiss, 1976, Science 192, 477-479). In this report, two monoclonal antibodies specific for antigens localized in the CNS of Drosophila melanogaster are utilized to examine the behavior of these neuronal antigens during metamorphosis. One of the antigens studied is concentrated in synaptic areas of the CNS in adults and larvae. The other antigen is more ubiquitously distributed, being present in both cortical and synaptic regions. Metamorphosis is accompanied by dramatic change in the concentration of the antigen localized to synaptic areas. In contrast, the ubiquitously present antigen persists throughout.