We show that two promoters of different strengths are involved in the tissue-specific expression of the alpha-amylase gene Amy-1a in the parotid gland and the liver of mouse. The weaker of the two promoters directs the synthesis of mRNA with a liver-type leader sequence. This promoter is active in both tissues. A promoter that is about 30-fold stronger is exclusively active in the parotid, where it directs the synthesis of an mRNA with a parotid-specific leader sequence. Neither the parotid nor the liver promoter is used in tissues that do not contain cytoplasmic alpha-amylase mRNAs, such as brain, kidney, and spleen. Nuclear transcripts that are initiated several kilobases upstream of the parotid cap site are detected in several tissues. They are most abundant in brain, and are apparently not processed into alpha-amylase mRNA.