A B S T R A C T To test the hypothesis that in both the liver and renal cortex ofthe fructose-loaded rat, severity of depletion of inorganic phosphate (Pi), and not the magnitude of accumulation of fructose-l-phosphate (F-1-P), determines the severity of the dose-dependent reduction of ATP, we intraperitoneally injected fed rats with fructose, 20 and 40 umol/g, alone, and at the higher load, in combination with (a) sodium phosphate, 20 umol/g, administered shortly beforehand or subsequently or, (b) adenosine, 2 ,umol/g, administered beforehand. The following observations were made: (a) With fructose loading alone, at the higher load, both Pi and total adenine nucleotides (TAN) were reduced by one third in the renal cortex and (as previously observed) by two thirds in the liver; and at either load, the reduction of ATP (and TAN)