Interferon‐α (IFN‐α) is an important molecule in the antiviral response, but cells from HIV‐1‐infected individuals show a reduced ability to secrete IFN‐α. We investigated an association between an imbalance of type 1/type 2 cytokines and the production of IFN‐α in HIV‐1 infection. We used whole blood culture to study the cytokine production profile, interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4), in response to HIV‐1 antigens and to study the Sendai Virus and HSV‐1‐induced‐production of IFN‐α in seven HIV‐1‐infected patients. An impaired synthesis of IFN‐α was obtained in patients with a predominant IL‐4 production (IL‐4 > IFN‐γ), and we found a positive correlation between the ex vivo production of IFN‐α and the IFN‐γ/IL‐4 ratio but not with the HIV RNA copy number in plasma. We investigated the role of T‐cell‐derived cytokines in the in vitro production of IFN‐α by PBMC from eight healthy donors, activated with Sendai Virus or HSV‐1. Whereas type 2 cytokines (IL‐4, IL‐13) inhibited virus‐induced IFN‐α synthesis, on the contrary, type 1 cytokines (IL‐2, IFN‐γ) enhanced it. A disarray in the T‐cell‐derived cytokine response may play a role in the defect of IFN‐α production in HIV‐1‐infected individuals. Further investigations are needed to explore this hypothesis.