This study evaluated total lymphocyte count (TLC) as a substitute marker for CD4+ cell counts to identify patients who need prophylaxis against opportunistic infection (CD4 < 200 cells/mm(3)) and patients with CD4 < 350 cells/mm(3) (Brazilian threshold value of CD4 count to define AIDS). We evaluated TLC and CD4+ cells count of 1,174 HIV-infected patients, in Salvador, Brazil, from May 2003 to September 2004. CD4+ cell counts were performed by flow cytometry, and TLC was measured with an automated hematological counter. The mean CD4 count was 430 cells/mm(3) (range: 4 to 2,531 cells/mm(3)). Mean TLC was 1,900 cells/mm(3) (range: 300 to 6,200 cells/mm(3)). Using a threshold value of 1,000 cells/mm(3) for TLC, the positive predictive value (PPV) was 77% for CD4 < 200 cells/mm(3), but the sensitivity was only 29%, while the negative predictive value (NPV) was 88%, with 98% specificity. Similar findings were observed for CD4 count < 350. Using the same threshold value of 1,000 cells/mm(3) for TLC, sensitivity was 14%, and specificity 99% (PPV= 94%; NPV=62%). In 70/1,510 (5%) of the samples the sum of CD4 and CD8 cell counts was greater than the TLC and in 27% (419/1,510) this sum was below 65% of the TLC. TLC has a high specificity to identify patients for prophylaxis, but a quite low sensitivity. It is not useful as an alternative to CD4+ T-cell counts as a marker in HIV-infected patients.