Mice aged 4 or 8 weeks were fed with a low-Mg2+ diet for 1, 2, 3 or 4 days. After 1 day of diet, the urinary excretion of Mg2+ and Ca2+ was strongly reduced in both animal groups (4 and 8 weeks), accompanied by a significant fall in plasma Mg2+ concentration and an increase in urinary volume. This profile persisted after 2, 3 or 4 days of dietary Mg2+ restriction. After 1 day of diet, transepithelial ion net fluxes of Na+, Cl-, Ca2+ and Mg2+ (JNa' JCI, JCl, JMg) measured in vitro from isolated perfused cortical thick ascending limbs (CTALs) of these animals remained unchanged. After 2 days of diet, measurements of J(Ca) and J(Mg) in isolated perfused CTALs showed that transepithelial Mg2+ and Ca2+ reabsorption were enhanced in CTALs from Mg(2+)-depleted, 8-week-old animals, whereas transepithelial Mg2+ and Ca2+ transport were not altered in 4-week-old mice. JNa and JCl and the transepithelial potential (PDte) were not modified in CTALs from either animal group. Our results suggest that a low-Mg2+ diet leads to urinary retention of Mg2+ and Ca2+ which is most likely due to increased Mg2+ and Ca2+ transport in the CTAL. Furthermore, in response to dietary Mg2+ restriction, the reabsorption of divalent cations in the CTAL of adult, but not of young, mice undergoes cellular adaptation.