Host factors which control replication and clearance of human immunodeficiency virus (HIV) are poorly understood. RANTES (regulated on activation, normal T cell expressed and secreted) and other beta-chemokines may be HIV-1-suppressive factors but their role in the progression of HIV-1 infection is a subject of controversy. We investigated the relationship between production of RANTES and correlates of disease progression in 15 patients infected with HIV-1. We used whole blood culture to study the production of RANTES, interferon (IFN)-gamma, interleukin (IL)-4 and IL-13 in response to supernatant of T cells infected with HIV-1. A defect of RANTES production was associated with a predominant type 2 and decreased type 1 cytokine profile (IL-4 and/or IL- 13 > IFN-gamma). We obtained a positive correlation between RANTES and IFN-gamma (P = 0.004) and the ratio of type 1 and type 2 cytokines IFN-gamma/IL-4 (P = 0.04) and IFN-gamma/IL-13 (P = 0.003), and a negative correlation between RANTES production and HIV-1 RNA copy number in plasma (P = 0.01). The same pattern of correlation was observed between HIV-1 p24-stimulated production of RANTES and the plasma viral load (P = 0.02, n = 15). The measurement of RANTES produced by heparinized whole blood in response to HIV-1 antigens appears as a potentially valuable tool to assess the defect of type 1 immune response in individuals infected with HIV-1 and to define whether the absence of a RANTES response may play a role in the increased rate of HIV-1 replication.