Although leptospirosis is a globally important zoonotic disease that affects humans on all continents, in both urban and rural areas, it often goes undiagnosed because its clinical manifestations are frequently non-specific. Even when leptospirosis is suspected, confirmation is made difficult by problems in isolating the causative organism in culture and by the low sensitivity of the available serological tests. Following torrential rains and flooding in January-February 2005, an outbreak of leptospirosis was suspected in Guyana, South America. Overall, 108 suspected cases presented at a medical post in the East Coast area of Guyana, and some of these cases are described in detail here. A better understanding of the clinical and paraclinical characteristics of leptospirosis should improve the recognition and appropriate treatment of the disease. Health education could reduce exposure, and physicians and primary healthcare workers could be made more aware of the signs and symptoms of leptospirosis.