Depletion of CD4+ T cells is one of the hallmarks of progression of HIV-1 infection. However, measurement of the CD4+ T-cell count is expensive and often unavailable in less developed areas. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4+ T-cell count. To determine the relationship between TLC and CD4+ T-cell count in HIV-1-infected South African patients, 2777 HIV-1-seropositive patients visiting the Immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa from April 1991 to April 1997 were included in the study. In total, 3237 observations were used to determine sensitivity, specificity, and likelihood ratios, with 95% confidence intervals, of various cutpoints of the TLC to predict an absolute CD4+ T-cell count of <200 cells/mm3, CD4+ percentage <20%, and CD4+ percentage <15%. Spearman rank correlations were calculated between TLC and CD4+ T cells, CD4+ percentage and CD8+ T cells, as well as between CD4+ and CD8+ T cells. Results demonstrated that a TLC of 2 × 109/L or less had a sensitivity of 90.3% to detect patients with a CD4+ T-cell count of <200 cells/mm3, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. For the observations as a group, a correlation (r = 0.704) between CD4+ T-cell count and TLC was demonstrated, but if the patients were divided into three groups according to their CD4+ T-cell count, this correlation weakened considerably. Therefore, although TLC shows a correlation with CD4+ T-cell count, it is not a good predictor of the CD4+ T-cell count in this population and should preferably not be used in the clinical care of HIV/AIDS patients.