Thin cortical tissue explants from kidneys of hydronephrotic mice were excised and incubated in different culture media containing growth and proliferation factors. Over a period of several months the content of renin in the explants and in the culture medium was repeatedly measured, to define the conditions necessary for the maintenance of renin production in a long-term culture. The best results were obtained when culturing the renal tissue in Dulbecco's medium (DMEM) with 10% fetal calf serum, 6 units/100 ml platelet-derived growth factor and 200 ng/ml glycylhistidyllysine. Renin was still present within the cells and in the culture medium after more than six months. Prevention of dedifferentiation, as evidenced in this case by the maintenance of renin production, seemed to be dependent on specific extracellular matrix proteins of renal origin. If the explants were dissociated from their matrix components by collagenase, a gradual loss of renin production was observed within 5 days. Complementation of the collagenase-digested cell suspension with different nonrenal extracellular matrix materials did not afford the stabilizing effect of the original pericellular matrix.