Replication capacity and transmission of human immunodeficiency virus (HIV)-1 in antiretroviral drug-naive Malawian women who had subtype C infection were investigated. Infant children of these women received either 1 dose of nevirapine or 1 dose of nevirapine plus 1 week of daily doses of zidovudine. PhenoSense HIV was used to determine replication capacity in 49 women whose infants were infected with HIV-1 and in 47 women whose infants were uninfected by 6-8 weeks of age. Mean replication capacity was higher in transmitters than in nontransmitters (P=.01). In a multivariate model, higher replication capacity was associated with transmission (odds ratio, 1.45 for each 10% increase in replication capacity [95% confidence interval, 1.11-1.90]; P = .0063), after adjustment for maternal HIV-1 load and other factors.