CD4+ T-lymphocyte (CD4) counts are a standard laboratory marker of disease progression in HIV infection, but expense precludes their use in large parts of the world. Total lymphocyte counts (TLC), in contrast, are widely available. We compared CD4 and TLC counts as predictors of developing AIDS or death in 831 HIV-positive out-patients (582 males and 249 females with both homosexual (males, n = 316) and heterosexual (n = 515) transmission patterns. The first CD4 count < 200/microliter and first TLC < 1250/microliter predicted similar (p = 0.52) survival, irrespective of clinical stage. For each clinical stage, a significant difference in progression to AIDS and mortality was predicted by TLC above or below 1250/microliter (p < 0.03). Survival and progression to AIDS occurred at similar rates in patients with a TLC < 1250/microliter or a CD4 count < 200/microliter (p > 0.1), and patients with a TLC > 1250/microliter or a CD4 count > 200/microliter (p > 0.5). A TLC < 1250/microliter preceded the development of Pneumocystis carinii pneumonia or cerebral toxoplasmosis in 76% of patients. In this longitudinal study, TLC and CD4 counts were equal predictors of disease progression. A TLC < 1250/microliter could be considered an indication for commencing cotrimoxazole prophylaxis.