Muscle cells were incubated with extracts prepared from neural tissue to investigate the mechanisms and factors which regulate mRNA transcript production of the alternatively spliced alpha-tropomyosin (alpha-TM) gene. Results from RNA analyses demonstrate that alpha-TM transcripts are dramatically altered by decreasing the production of the striated specific isoform while concomitantly increasing a cytoplasmic isoform. The factors which regulate alpha-TM expression are derived from neural tissue and act at the post-transcriptional level through a trans-activation mechanism. Furthermore, these factors can also alter the expression of alpha-TM mRNA isoforms in both non-muscle and primary muscle cells by regulating the exon splice site selection determined by endogenous trans-acting factors and force the production of a specific cytoplasmic isoform. The results demonstrate that the neural factors which regulate alpha-TM expression act through mechanisms and processes which are common to many different cell types and cell lineages.