The PSD-95 family of membrane-associated guanylate kinase (MAGUK) proteins are involved in the assembly and organization of neurotransmitter receptors at excitatory synapses in the vertebrate nervous system. We have isolated partial cDNAs for five PSD-95 family members from Apteronotus leptorhynchus brain RNA using a degenerate PCR method. The amino acid sequences deduced indicate that A. leptorhynchus neurons express homologues of the mammalian PSD-93, SAP-97, and SAP-102 MAGUKs and two homologues of mammalian PSD-95. In situ hybridization experiments have been carried out to localize the cellular expression of all five MAGUK mRNAs in the central nervous system of A. leptorhynchus. In the cerebellum the expression patterns are highly similar to patterns reported for mammalian cerebellum, suggesting an evolutionary conservation of the functional roles in this gene family. Cellular levels of expression of the PSD-95 MAGUK mRNAs and the NMDAR-1 mRNA were highly correlated in neurons of the dorsal forebrain but were not correlated in neurons of the electrosensory lateral line lobe (ELL) or the cerebellum. These results suggest that the expression of PSD-95 MAGUK genes in forebrain neurons may provide mechanisms for synaptic organization that are not shared by neurons in the ELL and cerebellum.