Antibody responses were studied in human patients from whom leptospiral serovars--mainly pomona or hardjo--had been isolated and identified. The antibody to the polysaccharide F4 antigen belonged exclusively to the IgM class, even as late as 10 months after infection. Human sera cross-reacted widely with F4 antigen from heterologous serovars. The antibodies involved in leptospiral agglutination were mainly IgM, but some patients also produced IgG agglutinins. The titres of IgM agglutinins were higher than those of IgG agglutinins and persisted for many months, regardless of the presence or absence of IgG agglutinins. Both types of immunoglobulin from patients with serovar pomona infection protected hamsters against lethal infections with homologous leptospires. The hamster-protective capacity of human sera correlated well with agglutinin titres. Sera from patients infected with serovars other than pomona protected hamsters against challenge with pomona only if they contained agglutinins to that organism.