The long-term prognosis of furosemide-associated nephrocalcinosis in the infant is still unclear. Although discontinuation of the diuretic often results in radiological resolution of the calcifications, functional abnormalities may persist. The natural history of the renal histopathology of these patients is yet unknown. In the present study we investigated the histological long-term outcome of furosemide-induced nephrocalcinosis in the young rat. Thirty-six weanling male Sprague-Dawley rats were divided into three groups: A controls, B furosemide given for 8 weeks, and C furosemide given for 2 weeks followed by 6 weeks of observation. Metabolic studies at the end of the experiment demonstrated a significant diuretic and natriuretic effect in group B. Kidney histology showed nephrocalcinosis scores (mean +/- SD) of 0.0 +/- 0.0 in A, 2.6 +/- 1.5 in B, and 0.8 +/- 0.6 in C, with B significantly higher than A and C, and C greater than A. Kidney calcium content in B (3,421.9 +/- 2,558.7 micrograms/g dry tissue) was significantly greater than in A (310.4 +/- 21.3) and C (1470.1 +/- 932.2). Another group of 6 rats receiving 2 weeks treatment of furosemide showed a nephrocalcinosis score of 2.2 +/- 1.5, not different from group B, and an additional group of 6 rats treated with furosemide for 2 weeks and observed for another 12 weeks showed a score of 1.3 +/- 0.4, not different from group C. We conclude that most of the renal calcifications induced by furosemide occur during the early days of treatment and that up to 12 weeks after discontinuation of the diuretic, the resolution of the calcifications is only partial.