The GTPase activating protein-related domain (GRD) of the human neurofibromatosis type 1 gene (NF1) was shown to have two types of splice variants. Through polymerase chain reaction (PCR), we isolated and sequenced three types of splice variants in the rat NF1-GRD. Type I and II transcripts were highly homologous with the human transcripts. The type III NF1-GRD transcript, unidentified in the human, had an additional 41-bp insert immediately downstream from the 63-bp insert of the type II transcript. The type III transcript encoded for a protein that prematurely terminated its predicted amino acid sequence because of a stop codon, resulting in possible modification of the GAP activity. All three transcripts were found in the rat's liver, cerebral hemispheres, spinal cord, colon, and spleen, whereas the other organs examined had only type I and II transcripts. This differential splicing mechanism may regulate the activity or compartmentalization of the NF1 protein, resulting in modulation of the Ras-related signal transduction pathway.