Host genetic factors may influence the course of human immunodeficiency virus (HIV) infection. In Blantyre, Malawi, polymerase chain reaction was used to identify twin pairs who were concordantly HIV-1-infected in utero or perinatally and then to examine strain divergence or virus levels in identical and fraternal twin pairs. Among 315 twin pairs, both infants in 14 fraternal and 5 identical pairs were found to be infected at the same visit. Among 10 pairs, HIV-1 sequences were determined for both infants at >or=1 time point. HIV levels had a common profile in both fraternal and identical twin pairs. Identical twins were not always infected by the same quasi species, indicating that their mothers had multiple quasi species capable of infecting their infants. Subsequent viral divergence appears to depend on quasi-species stability rather than on genetically controlled host immune responses. Thus, given infection, factors intrinsic to HIV-1 are more important than host genetics in viral evolution.