BACKGROUND: Patients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency. Previous data suggest that such patients may have diminished capacity for CD4 cell count recovery. METHODS: Rates of CD4 cell increase were determined over 48 weeks among ART-naïve individuals (n = 596) commencing ART in a South African community-based ART programme. RESULTS: The CD4 cell count increased from a median of 97 cells/microl at baseline to 261 cells/microl at 48 weeks and the proportion of patients with a CD4 cell count < 100 cells/microl decreased from 51% at baseline to just 4% at 48 weeks. A rapid first phase of recovery (0-16 weeks, median rate = 25.5 cells/microl/month) was followed by a slower second phase (16-48 weeks, median rate = 7.7 cells/microl/month). Compared to patients with higher baseline counts, multivariate analysis showed that those with baseline CD4 counts < 50 cells/microl had similar rates of phase 1 CD4 cell recovery (P = 0.42), greater rates of phase 2 recovery (P = 0.007) and a lower risk of immunological non-response (P = 0.016). Among those that achieved a CD4 cell count > 500 cells/microl at 48 weeks, 19% had baseline CD4 cell counts < 50 cells/microl. However, the proportion of these patients that attained a CD4 count 200 cells/microl at 48 weeks was lower than those with higher baseline CD4 cell counts. CONCLUSION: Patients in this cohort with baseline CD4 cell counts < 50 cells/microl have equivalent or greater capacity for immunological recovery during 48 weeks of ART compared to those with higher baseline CD4 cell counts. However, their CD4 counts remain < 200 cells/microl for a longer period, potentially increasing their risk of morbidity and mortality in the first year of ART.