Large-restriction-fragment pattern comparison of Mycobacterium avium from 85 blood, stool, and respiratory specimens from 25 human immunodeficiency virus-infected San Francisco patients revealed 4 strains that infected multiple people (3 groups of 2 patients and 1 group of 3 patients). Most patients harbored a single M. avium strain, but 2 strains were recovered from 8 patients. The significance of recovering 2 strains is not clear, since the second strain was seldom recovered more than once. The strain recovered from blood was recovered from stool of 4 patients and respiratory secretions of 6 patients >4 weeks before detection of bacteremia, indicating that the intestinal and respiratory tracts are entry portals from which M. avium can disseminate. M. avium from 21 cities outside of California served as controls. Thus, a single M. avium strain can cause disseminated infection in multiple patients. This may represent infection from a common environmental source or person-to-person spread.