In March-April 1998 in a neighborhood in the city of Santa Fe, Argentina, there was an outbreak of an acute disease characterized by fever, headaches, and intense myalgias. This article presents the studies surrounding this outbreak and the attempts to identify the source and the mode of transmission. The epidemiological, serological, and clinical findings indicated that the causative agent was Leptospira interrogans. As a screening test, macroscopic agglutination with heat-resistant antigen was applied, followed by the ELISA test, and, as a confirmatory test, microscopic agglutination for 10 serotypes of L. interrogans. The study covered 32 persons, 8 dogs, and 8 water samples. Among the 32 persons, 12 cases were confirmed, 2 were suspicious, and 18 were negative. Six dogs were found to be infected, and motile spirochetes were found in the water samples. The human sera reacted with the ballum, canicola, icterohaemorrhagiae, and pyrogenes serotypes; the canine sera reacted with the ballum, canicola, and pomona serotypes. The coagglutination found in all the confirmed cases indicates that they were acute cases of leptospirosis, but it was impossible to identify the causal serotype. Except for the index case, the disease was not recognized clinically. Several facts suggest that the outbreak was caused by rain that had flooded the study area. The results of this study emphasize the need for active surveillance of leptospirosis when there are floods and other natural disasters.