GB virus type C (GBV-C) infection was studied in a convenience sample of 75 antiretroviral (ART)-naive African mothers with human immunodeficiency virus infection and their infants. GBV-C RNA was extracted from serum and amplified by reverse-transcriptase polymerase chain reaction. Twenty-seven (36%) of these 75 HIV-infected women tested positive for GBV-C RNA. To study transmission dynamics, we chose a random subsample of 20 of these women and their infants. In this cohort, there was evidence of postnatal transmission of GBV-C; however, it was not possible to demonstrate evidence of in utero or intrapartum transmission. In this pilot observational study, transmission of HIV from mother-to-infant occurs independently of the GBV-C infection status of the mother. The immunological indices measured tend to suggest an association with protection and or delayed progression of HIV disease in GBV-C-infected mothers.