The natural history of enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) infection was studied among 40 US travelers who provided weekly stool samples for 4 weeks after arrival in Mexico. At enrollment, 5 subjects were colonized by EAEC and 3 by ETEC. During the first 2 weeks after enrollment, 12 developed EAEC diarrhea, 7 developed ETEC diarrhea (5 with mixed EAEC/ETEC diarrhea), 13 had EAEC colonization, and 7 had ETEC colonization. During the third and fourth weeks, 4 experienced EAEC diarrhea, 2 experienced ETEC diarrhea (1 with mixed EAEC/ETEC diarrhea), 31 had EAEC colonization, and none had ETEC colonization. Plasmid DNA analysis showed a high degree of heterogeneity among EAEC isolates. Symptomatic EAEC infection occurred early after arrival in Guadalajara, Mexico, and was as common as ETEC infection. Asymptomatic EAEC infection was recurrent.