A 52-year-old man with a history of HIV (CD4 count 155, and viral load 154 K), who is on antiretroviral treatment presented in the emergency room with acute onset of headache. The patient had lumbar puncture and found to have elevated intracranial pressure and cryptococcal antigen was positive. The patient was started on flucytosine. After 10 days of treatment, the patient developed watery diarrhoea. An extensive infectious workup was carried out, which did not reveal any infectious aetiology. A colonoscopy was carried out which revealed acute colitis in the colon and the pathology confirmed the colonoscopic findings with severe colitis in the colon. At this time, the patient's diarrhoea was attributed to flucytosine and it was stopped. The patient's diarrhoea improved after 5 days of stopping flucytosine.