Diuretics are known to cause magnesium depletion, and the aim of the present experiment is to establish the relationship between lymphocyte magnesium concentration and intracellular magnesium concentration during chronic diuretic therapy. Studies were conducted in male Wistar rats that were subjected to daily administration of furosemide (2 mg/kg/day IP) for 19 weeks. Clearance measurements were performed during the baseline week and subsequently during the third, seventh, eleventh, fifteenth, and nineteenth weeks in both furosemide-treated (n = 32) and control rats (n = 32). Lymphocyte magnesium concentration was also measured as a determinant of intracellular magnesium concentration. Magnesium concentrations in kidney, bone, skeletal, and heart muscle tissues were also quantitated at week 11 and at the end of the experiment. After 11 weeks of furosemide administration, furosemide-treated rats developed a lower plasma magnesium concentration (0.95 +/- 0.01 mmol/L) compared with that in the control group (0.99 +/- 0.01 mmol/L). This difference persisted from week 11 to week 19 of the experiment. Fractional excretion of magnesium was modestly elevated in the furosemide-treated group. After 7 weeks of furosemide treatment, lymphocyte magnesium concentration decreased significantly in furosemide-treated rats when compared with that in the control group (1.56 +/- 0.09 micrograms/mg protein vs 1.33 +/- 0.07 micrograms/mg protein). During week 19, the lymphocyte magnesium concentration had fallen to 0.75 +/- 0.04 micrograms/mg protein as compared with 1.45 +/- 0.08 micrograms/mg protein in the control rats. There is a significant correlation between lymphocyte magnesium concentration and plasma magnesium concentration. Our present results indicate that during long-term diuretic therapy, lymphocyte magnesium concentration mirrors the reduction in plasma magnesium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)