On July 1, 2011, two Australian male tourists aged 25 and 26 years were admitted to the emergency department of the Careggi Hospital, Florence, Italy, reporting a 1-week history of fever with sudden onset of headache, myalgia, nausea, vomiting, and diarrhea. They had no significant past medical or surgical history and they had recently traveled from Venice to Florence. At the time of admission they showed similar clinical signs and symptoms, mainly jaundice, conjunctival hyperemia, and muscle tenderness. Routine hematological and biochemical profiles were similar (Table 1). In both cases laboratory findings evidenced acute renal failure and hepatic impairment. Vital signs were normal. On auscultation, the heart sounds had no abnormalities and air entry was equal on both lungs with occasional scattered wheezing. Results of neurological examination were normal. Electrocardiogram, abdominal ultrasound, and X-ray of the chest revealed no abnormalities. Asked about recent exposure to animals, mud, or potentially contaminated freshwater sources, the young tourists mentioned they had settled at a campsite near Venice 2 weeks earlier; because of the heat, they had both immersed their feet in the waters of a Venice canal close to Rialto Bridge. One of them had also swum in it for less than a minute without any protection for the conjunctiva. No skin lesions or trauma were observed at the time of possible infection, nor any swallowing of the canal water. The common history of exposure to possible contaminated water, along with hepatic and renal impairment, suggested the diagnosis of leptospirosis. However, blood and urine specimens were collected for culture and polymerase chain reaction (PCR) was also evaluated. Serum samples were tested by the microscopic agglutination test (MAT). Intravenous ceftriaxone (2 g every 24 h) was empirically administered. Adequate fluids and a diuretic infusion were also started. Both patients required daily hemodialysis for 5 days as a result of the severe renal injury. Blood and urine cultures had no growth. The PCR result was positive for leptospiral DNA in the urine of both patients. First collected serum sample results (approximately the tenth day of disease) were positive by MAT in both subjects with titers to serovars icterohaemorrhagiae of 1 : 1,600 and serovars copenhageni of 1 : 200 (serogroup icterohaemorrhagiae). Serovars icterohaemorrhagiae and copenhageni are commonly associated with rats as reservoir hosts. Ten days later, the titer of 1 : 1,600 was confirmed in the first subject, while that of 1 : 200 of the other attained 1 : 3,200 (Table 1). The clinical picture progressively improved, restoring normal function of liver and kidney, and they were discharged after 2 weeks.