c-ErbB2 (also referred to as Neu or HER2), a transmembrane glycoprotein with intrinsic tyrosine kinase activity, is structurally related to epidermal growth factor receptor (EGFR) and forms active heterodimers with EGFR as well as other members of the EGFR family. c-ErbB2 is reported to mediate differentiation and proliferation in epithelial cells and is expressed in a tissue-specific and developmental stage-specific manner. Given the role of EGFR in cystic renal epithelial hyperplasia and the immature phenotype of cystic renal epithelial cells, the segment-specific expression pattern of c-ErbB2 in human autosomal recessive polycystic kidney disease (ARPKD) was examined in nine ARPKD kidney specimens ranging from gestational age 17 wk through postnatal age 4 wk. c-ErbB2 staining of human ARPKD samples showed increased expression with increasing gestational age compared with normal human fetal and postnatal kidneys. This increased c-ErbB2 expression was primarily localized to the apical surfaces of cystic collecting tubule cells, similar to the pattern of EGFR expression, and paralleled collecting tubular cyst formation and growth.