Micropuncture and clearance studies were performed on rats with chronic metabolic acidosis to evaluate the segmental handling of magnesium. Fractional magnesium excretion was 12.6 +/- 2.3% in acidemic rats (blood pH 7.17 + 0.2) compared to 5.1 +/- 1.3% of normal animals (blood pH 7.36 +/- 0.05). Ultrafiltrable magnesium concentrations were similar in both normal and acidotic animals, 0.51 +/- 0.02 and 0.48 +/- 0.03 mM, respectively. Elevation of urinary magnesium excretion was due to diminished reabsorption in the loop of Henle and segments beyond the distal sampling site. Acute correction of the systemic acidosis with NaHCO3 infusions partially corrected the renal magnesium levels as fractional magnesium excretion fell from 12.6% to 3.1 + 0.75%. This was associated with enhanced reabsorption of magnesium in the loop. To determine if acidosis may compromise the renal conservation of magnesium, acidotic rats were subsequently placed on magnesium-restricted diets. Normal and acidotic animals adapted appropriately and to a similar extent when challenged by short-term magnesium-restricted diets. Accordingly, elevation of dietary acid intake and systemic acidosis leads to renal magnesium wasting which is due in part to diminished reabsorption in the loop of Henle. However, chronic acidosis does not compromise the renal adaptive response to dietary magnesium restriction.