The aim of this study was to investigate if the risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is influenced by the biological phenotype of the mother's virus. Virus isolates from 30 HIV-1 infected mothers and 12 infected children born to these mothers were analyzed for replication on several cell lines (Jurkat-tat, Jurkat, CEM, U937 clone 2, and MT-2). We show that mothers who harbor virus able to replicate in cell lines (rapid/high virus) have a significantly higher risk to infect their children than mothers with slow/low virus (P = 0.017). Children born to mothers with rapid/high viruses can be infected by slow/low as well as rapid/high viruses, while mothers with slow/low virus appear to transmit slow/low virus in every case. Our study shows that the biological phenotype of the mother's virus may serve as a complementary marker to CD4+ lymphocyte counts and p24 antigenemia in predicting the risk of transmission of HIV-1 to the child.