In an attempt to explain the triamterene stone diathesis, we studied the excretion and solubility of triamterene, 1, and its metabolite, the sulfate ester of the hydroxy derivative of triamterene, 3. The urinary excretion pattern and metabolism in stone formers was the same as in other chronic users of triamterene or healthy volunteers. The solubility of triamterene in urine was approximately one-half of its solubility in buffer solution, whereas the sulfate ester, 3, was nearly twice as soluble in urine as in the buffer solution. In the majority of the subjects studied, we found concentrations of 3 which approached or exceeded apparent solubility limits in urine. This was not true for triamterene where most measured urine concentrations were less than the apparent solubility as determined by equilibration. Alteration in the metabolism of triamterene is probably not a causative factor for triamterene nephrolithiasis. The saturation of urine with triamterene and especially with the sulfate ester, 3, may be related to stone formation, but other physical factors play a role in determining the relative amounts of drug found in calculus material.