The immunohistochemical expression of the trophic peptide insulin-like growth factor I (IGF-I; somatomedin C) was investigated in the post-ischaemic regenerating rat kidney. The part of the nephron most severely injured by the ischaemic insult was the pars rectae or S3 region of the proximal tubules. In this part of the nephron no specific IGF-I immunoreactivity could be demonstrated under control conditions. Three days after injury, however, low regenerating tubular cells expressing IGF-I immunoreactivity could be demonstrated invading the damaged region. Five and 7 days post-ischaemia some of the regenerating cells showed IGF-I immunoreactivity while adjacent and similar-looking cells did not. In parallel with an increasing differentiation of the regenerating cells the IGF-I immunoreactivity vanished. Fourteen days after the injury the S3 cells had regained their normal morphology, and by this time the IGF-I immunoreactivity had returned to a normal undetectable level. It is concluded that there is a transient increase in the expression of IGF-I mainly confined to the early phase of post-ischaemic rat kidney regeneration. It is proposed that IGF-I exerts its trophic role by paracrine mechanisms.