A natural history study of pneumococcal infection in 82 infants followed from birth is reported. Longitudinal carriage patterns were determined by serial throat and nasopharyngeal cultures. Seventy-nine of 82 infants carried one or more types during the study period. The first type was acquired by a mean age of six months, and the duration of carriage decreased with successive types carried. Acquisition of new types peaked in winter months, but carriage rates fluctuated throughout the year. Thirty-one pneumococcal infections were documented in 24 infants: 28 episodes of otitis media, two of bacteremia, and one of meningitis. Types causing disease were similar to commonly carried types (6, 14, 19, and 23). However, infection usually occurred within one month of acquisition of a new type and was seldom associated with prolonged carriage. In terms of exposure to new strains, 15% (31 of 196) of acquisitions resulted in disease.