Histoplasmosis is an opportunistic infection affecting those with weakened cellular immunity. Suppression of cell mediated immunity after transplant can allow unchecked progression of this disease. A 41-year-old male patient from North India was di-agnosed with localized histoplasma infection (Cheek region) based on biopsy at 1.2 years after renal transplant. This localized infection was treated with reduction of immunosuppressive medication (mycophenolate) and itraconazole. Upon resolution of symptoms itraconazole was stopped by local physician and immunosuppressive medications reinstalled after 3 weeks. Three years after transplant patient again presented with multiple painful skin lesions with bony involvement (right ulna and left tibia). Biopsy from skin and involved bone revealed histoplasma. Whole body PET scan revealed metabolically active disease. Diag-nosis of disseminated histoplasma was kept and started on liposomal amphotericin B (induction) and itraconazole (maintenance for 1 year) with itrconazole drug level monitoring. Also immunosuppression was reduced (mycophenolate stopped). Follow-up MRI at 3 months showed size reduction of involved lesions but bone biopsy revealed persistence of histoplasmosis. During same time serum creatinine also rose from baseline of 1.2–1.4 mg/dL to 2.4 mg/dL. Renal graft biopsy revealed glomerular and vascular thrombotic microangiopathy (TMA). Based on clinical response, treatment was continued with plan for interval surveillance renal graft biopsy. Surveillance graft biopsy after 3 months showed resolution of TMA. The whole-body PET scan after 6 months of initial PET showed decrease in FDG avidity and extent of the lesions. At 9 months of treatment completion patient has a stable graft function with creatinine at 2.2 mg/dL to 2.4 mg/dL on tacrolimus and prednisolone. Itraconazole is being continued with therapeutic drug monitoring. Histoplasmosis, particularly if involving bone, is slow to respond to antifungal therapy. Prolonged therapy with therapeutic drug monitoring, ideally supported by culture and sensitivity reporting, is the sine qua non of histoplasma treatment. Disseminated histoplasmosis can cause TMA which regresses on treating histoplasmosis.