Furosemide, a potent natriuretic agent, is well known to increase urinary calcium excretion. We study the effects of long term administration of furosemide on the calcium balance, renal function and histopathological changes of the kidneys and the parathyroid glands in the rat. Furosemide (20 mg/kg) was administered 3-4 times per week for 62 weeks intraperitoneally in 10 male rats. The same volume of normal saline was administered intraperitoneally in 9 male rats as control. All were given with standard diet (CE-2) and deionized water. While urinary calcium and creatinine were measured every 1-4 weeks, serum calcium and creatinine were measured in the first week and at the end of examination. 24 hours urinary excretion of calcium was elevated to two to three folds (a significant increase over the control: p less than 0.01) after the furosemide loading, though serum calcium and creatinine levels remained as in control. Despite a marked hypercalciuria in the furosemide loaded rats, there was no evidence of stone formation in the kidney or in the urinary tract. On histopathological examination renal parenchyma showed some pyelonephritic changes but without evidence of crystal formation, while no significant change was noted in the parathyroid glands. Based on these data we concluded that in our model, 1) there was a significant calcium loss in the absence of any change in the serum calcium, but 2) this hypercalciuria alone was not lithogenic, and 3) parathyroid glands showed no discernible secondary morphological changes.(ABSTRACT TRUNCATED AT 250 WORDS)