The known Duchenne muscular dystrophy (DMD) gene products, the muscle- and brain-type dystrophin isoforms, are 427-kDa proteins translated from 14-kilobase (kb) mRNAs. Recently we described a 6.5-kb mRNA that also is transcribed from the DMD gene. Cloning and in vitro transcription and translation of the entire coding region show that the 6.5-kb mRNA encodes a 70.8-kDa protein that is a major product of the DMD gene. It contains the C-terminal and the cysteine-rich domains of dystrophin, seven additional amino acids at the N terminus, and some modifications formed by alternative splicing in the C-terminal domain. It lacks the entire large domain of spectrin-like repeats and the actin-binding N-terminal domain of dystrophin. This protein is the major DMD gene product in brain and other nonmuscle tissues but is undetectable in skeletal muscle extracts.