The annual incidence of leptospirosis in Barbados is approximately 13 severe cases/100,000. The peak incidence occurs in October to December of each year, coinciding with the months of heaviest rainfall. During the second half of 1995, an epidemic of dengue type 1 infection produced almost 1,000 laboratory-confirmed cases. During the same period, leptospirosis mortality was twice the average, suggesting that some cases of leptospirosis were being misdiagnosed and treated inappropriately. Sera from patients investigated for dengue or leptospirosis were analyzed retrospectively to determine the extent of misdiagnosis. During 1995 and 1996, 31 of 139 and 29 of 93 patients, respectively, were confirmed as having leptospirosis. Sera from the remaining leptospirosis-negative patients were tested for IgM antibodies to dengue virus. During 1995 and 1996, 48 of 108 patients and 21 of 64 patients, respectively, were found to have dengue. In 1997, sera from all patients investigated for leptospirosis were also tested prospectively for IgM antibodies to dengue: 38 of 92 leptospirosis-negative patients (41%) were dengue IgM-positive, while 2 of 25 leptospirosis cases also had serologic evidence suggesting acute dengue infection. A second large outbreak of dengue caused by serotype 2 occurred in 1997. During the 1995 and 1997 dengue epidemics in Barbados, dengue cases outnumbered leptospirosis cases investigated in the leptospirosis diagnostic protocol. During 1997, patients investigated but negative for dengue were also tested for anti-leptospiral IgM: 7.3% (19 of 262) were IgM-positive. Substantial misdiagnosis of both dengue and leptospirosis can occur and greater public awareness and clinical suspicion of the similar presentations of these two diseases are necessary.