Studies on cultured human renin(R)-producing tumors cells are few. In this work the R secretion by a human juxtaglomerular tumor (JGT) in various tissue culture models was evaluated by a new immunoradiometric assay. Freshly isolated JGT cells actively secreted total R (tR; about 70% of which is proR) into the perfusion media of very short-term cultures (tR concentration, 100-400 ng/ml/10(6) cells), independently of factors stimulating or inhibiting R output by normal JG cells. Primary monolayer cultures of the same JGT rapidly lost their tR-secreting capability and died by apoptosis within two months. Conversely, a JGT explant survived for up to 22 months in vitro. During the first year of culture, this explant increased in volume and generated, at 3- to 4-monthly intervals, several self-limited cellular outgrowths, from which it became detached. Meanwhile, tR secretion by the explant decreased very slowly, though its decline was transiently and partly reversed by various combinations of growth factors, hormones, a prostaglandin, and selenous acid added to either a serum-enriched or a synthetic medium. By the 12th month in vitro, tR secretion had faded away. Like the primary monolayers, the various explant outgrowths, once detached, stopped secreting tR and died in a few weeks. Hence, the preservation of a histiotypic relationship and the actions of several mitogenic and/or differentiating agents are essential for the long-term survival and the continuance of R secretion by human JGT cells in vitro.