A hospital-based cohort study assessing the function of surrogate markers (beta 2-microglobulin and CD4/CD8 ratio) in predicting maternal HIV transmissibility and disease progression in infants was conducted in 110 seropositive black South African mother-infant pairs. There were no differences in beta 2-microglobulin (beta 2-M) levels between the 27 transmitting and 83 non-transmitting mothers (P = 36). beta 2-M levels were higher in the infected that in the uninfected infants, but were significantly higher at 1 month (P = 0.04) and again at 12 months (0.03). A CD4/CD8 ratio < 1 was increasingly reported in the infected infants from 3 months (60.9%) to 15 months (93.8%) of age, and in three (5.4%) uninfected infants. Of the eight infected infants who rapidly progressed to death by 9 months, increased beta 2-M levels at birth and 1 month and inverted CD4/CD8 ratios at 3 months were strongly associated with the objective morbidity score. However, the CD4/CD8 ratio (positive predictive value 82.4%, negative predictive value 82.8%) at 3 months or later remained a better indicator of disease progression than beta 2-M (positive predictive value 33.3%, negative predictive value 74.4%).