The ability of motile strains of the Ogawa and Inaba serotypes of classical Vibrio cholerae and of the El Tor biotypes to kill suckling mice after oral challenge with 10-8 colony-forming units (representing at least 100 to 1,000 minimal lethal doses) was compared to that of nonmotile derivatives of the same strains. Loss of motility, in each case, resulted in a marked reduction in virulence. The mortality (at 36 h) caused by 10 of the 13 nonmotile strains was 32% or less. whereas the motile wild-type strains resulted in nearly 100% deaths. The reduced virulence of the nonmotile strains was associated with reduced capacity to adsorb to the surface of segments of mouse intestine. The mutants were tested for alterations in enterotoxin production and surface properties. The results suggest that motility may contribute to virulence by increasing the chance for association of the vibrios with the intestinal mucosa.