EGF and TGF-α in the human kidney: Identification of octopal cells in the collecting duct. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α) are well-known mitogens expressed in the kidney. Their human renal cell origin has not been conclusively identified. The distribution of EGF and TGF-α was investigated immunohistochemically in the adult human kidney in comparison with the monkey and rodent kidney. In humans, as in the monkey, two variants of EGF immunoreactivity were detected. One was present along the apical cell surfaces and diffusely in the cytoplasm of the thick ascending limb (TAL), co-localizing with Tamm-Horsfall protein, and in the distal convoluted tubule (DCT). The other occurred as overall membranous staining in the connecting tubule and cortical collecting duct (CD), and mainly as basal staining in the rest of the CD. The EGF stained cells in the cortical and outer medullary CD reached a diameter of 40 µ and were identified as intercalated or dark cells; they displayed a peculiar octopus-like shape, bearing long lateral extensions that stretched underneath and between 20 surrounding smaller negative cells. Cytoplasmic TGF-α staining appeared in the DCT and decreased further on. In conclusion: (1) the normal human distal nephron displayed EGF and TGF-α immunoreactivity in a partly complementary segmental and subcellular distribution pattern, partly differing from that in rodents. (2) EGF immunostaining revealed the presence of long lateral projections on CD intercalated cells; this peculiar morphology suggests a modulatory role within the CD epithelium, possibly involving the EGF immunoreactivity on their surface.