The relationship of the neutralizing activity (NA) profile of sera from human immunodeficiency virus (HIV)-infected individuals to the HIV viral load and the absolute CD4 count was examined. The NA of 24 serum samples against autologous isolates (AI) and HIV type 1 strain MN was examined. Three NA patterns were recognized. Nine sera neutralized both AI and MN (+/+), six sera neutralized MN but not AI (/+), and nine sera failed to neutralize both AI and MN (/). The identification of the three neutralization patterns (+/+, /+, and /) indicated that resistance to neutralization was progressive. A reciprocal relationship between the viral burden of the patients and the NA profiles was observed. The nine subjects with a / NA profile had a plasma viral load of 5 × 10⁴ copies/ml and a cellular viral burden of 1,122 infectious units per million viable cells, which were significantly different from those of the other groups (P < 0.02). These patterns were independent of the phenotypic characteristics of the virus. Longitudinally, subjects with a / profile at baseline gained their HIV-specific NA by 24 weeks of antiretroviral therapy when this was associated with a 1-log₁₀ decline in the plasma HIV viral load. The sera from week 24 from some patients were able to neutralize both the 24-week and the baseline dominant virus isolates. A change in CD4 cell count of 50 or more in either direction predicted a / or +/+ profile. The verification of the autologous NA profile might be important in selecting patients who may benefit from immune-based therapies involving neutralizing monoclonal antibodies.