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In rats, single intravenous doses of folic acid induce damage to renal tubular epithelium, deposition of folic acid in tubular lumens, increase in wet kidney weight, oliguria and interstitial connective tissue proliferation. Separation of the nephrotoxic and obstructive effects of folic acid was attempted by pretreatment with NH₄Cl or NaHCO₃. These effects of folic acid were unaltered by pretreatment with NH₄Cl and there was, in addition, accumulation of eosinophilic droplets in papillary collecting duct epithelium. After pretreatment with NaHCO₃ folic acid deposition is decreased or absent; there is a smaller increase in wet kidney weight; the rats are Polyuric rather than oliguric; interstitial connective tissue proliferation is reduced; and no droplets form in papillary collecting ducts, but lesions are still present in proximal convoluted tubule epithelial cells. These findings indicate that folic acid has direct nephrotoxic effects …