Two patients developed symptomatic methemoglobinemia and hemolytic anemia after treatment with phenazopyridine. Methemoglobinemia appears to be a rare occurrence after commonly used doses of phenazopyridine; phenazopyridine-associated hemolytic anemia has been reported both after overdose and after usual doses. The presentation of methemoglobinemia in the first patient and the response to treatment with methylene blue in the second patient were unusual, suggesting that the patients had a red cell defect or were exposed to other oxidizing substances. One of the major metabolites of phenazopyridine is aniline, a known cause of methemoglobinemia. Aniline-induced methemoglobinemia is less responsive to treatment with methylene blue than nitrate- or nitrite-induced methemoglobinemia. This may explain, in part, the poor response to methylene blue by one of our patients.