Integrins are cell adhesion receptors that mediate cell-extracellular matrix and cell-cell interactions. Each integrin consists of two glycoprotein subunits (alpha and beta). We have previously described a novel integrin beta-subunit, beta6, which is expressed in cultured epithelial cells. Beta6 can associate with alphav to form the fibronectin-binding heterodimer alphavbeta6. Here we report the tissue distribution of beta6 integrin mRNA determined by in situ hybridization of a beta6 cRNA probe with representative frozen tissue sections from a rhesus monkey tissue bank. We detected beta6 mRNA exclusively in epithelial cells. However, beta6 mRNA expression varied greatly among different epithelia. High levels of beta6 mRNA were found only in two very specialized epithelial cell types: a portion of the kidney tubule epithelium, termed macula densa, and the endometrial epithelium of secretory phase uterus. In the endometrium, beta6 expression was highest in the differentiated epithelium of functional layer glands, suggesting that beta6 expression can be regulated in a differentiation-dependent manner. Beta6 expression may also depend on the stage in the estrous cycle, since we found much lower beta6 mRNA levels in a specimen of proliferative phase endometrium. Epithelium in several other tissues, including salivary gland ducts, gall bladder, and epididymis, contained detectable levels of beta6 mRNA, albeit much lower than in macula densa and endometrium. In other epithelia, including skin and lung, beta6 mRNA was undetectable. Taken together, these results suggest that in normal adult primates beta6 expression is regulated in a cell type-specific manner, restricted to a few epithelial tissues.