Dystrophin mRNA transcripts from the P (Purkinje) promoter were shown to be differentially expressed in human skeletal muscle, heart, and brain. The expression pattern was characteristic of tissue type and developmental stage. Polymerase chain reaction (PCR) analysis of the P promoter transcripts in adult skeletal muscle and adult brain identified two alternatively spliced sequences, one that encodes a full-length dystrophin mRNA and a second that transcribes a termination codon 27 nucleotides (8 amino acids) after the ATG initiation site. Alternative splicing of this truncated coding transcript was developmentally regulated, and it was expressed as the major form in adult cortical brain and adult heart. The biological significance of this peptide remains unclear. The full-length transcript was the major form in fetal cortical brain and adult skeletal muscle. Ribonuclease protection assay demonstrated that as much as 20% of dystrophin transcription in normal adult skeletal muscle was derived from the full-length transcript from the P promoter. In contrast, adult heart did not express significant levels of P promoter derived transcripts. Thus, transcripts from the P promoter were found to be developmentally regulated in the brain, and its activity was differentially expressed in skeletal versus cardiac muscle tissues. These data show that the P promoter transcript displays a broader scope of expression, regulation, and complexity than previously appreciated.