Exposure to mycotoxin producing mold and mycotoxins can be associated with numerous adverse health consequences. We previously reported that patients with chronic illness frequently had a history of prior exposure to water damaged buildings (WDB) and mold. Additionally, the vast majority of these patients had mycotoxins present in the urine. We have postulated that the mycotoxin producing molds were likely harbored internally in the sinuses of these patients. In the present analysis, patients with chronic illness and a positive urine mycotoxin assay were treated with intranasal antifungal therapy, either amphotericin B (AMB) or itraconazole (ITR). AMB was associated with local (nasal) irritation adverse effects (AE) in 34% of the cases, which resulted in discontinuation. In patients that remained on therapy without AE, we found that 94% improved clinically. Additionally, we found that the urine mycotoxin levels decreased substantially in patients that improved on therapy. Similar findings were seen with ITR, however the number of patients treated was much smaller.