Beginning in late December, 1975, almost one-third of the passengers on two successive cruises of a Miami-based cruise ship noted the onset of diarrheal illness while on board. A single serotype of Escherichia coli that produced heat-labile enterotoxin without producing heat-stable enterotoxin was recovered from the stool of most ill passengers cultured. Epidemiological investigation could not specifically define the mode of spread. The clinical picture presented was similar to the illness caused by enterotoxigenic E. coli that produce only heat-stable enterotoxin or that produce heat-stable and heat-labile enterotoxins.