In the context of clinical therapy with recombinant human interleukin‐2 (IL‐2), we monitored immunological alteration in 10 human immunodeficiency virus type‐1 (HIV‐1)‐infected individuals, on stable antiretroviral therapy, who had a CD4+ cell count between 200 and 500 cells/mm3. Subcutaneous IL‐2 was prescribed thrice weekly (at a dose of 3 × 106 IU) for 24 weeks and the patients were followed‐up for 32 weeks. IL‐2 treatment induced an increase in the CD4+ percentage (P < 0.001) and CD4+ cell count (P < 0.009). Furthermore, natural killer (NK) cell activity was increased (P < 0.001) at week 8 of treatment, whereas lymphokine‐activated killer (LAK) cell activity showed a transient, nonsignificant increase at week 8 and was reduced (P < 0.001) at 32 weeks. However, the cytotoxic T‐lymphocyte (CTL) activity decreased against HIV antigens, and the proliferative response to Candida, IL‐2 and phytohaemagglutinin (PHA) declined during the first 8 weeks (P < 0.05) and returned to baseline levels after 32 weeks. The HIV RNA level did not change during IL‐2 therapy; however, after 8 weeks of follow‐up a significant increase (P < 0.001) in viral load was observed. In conclusion, continuous IL‐2 treatment to HIV‐infected individuals enhanced the CD4 count, but the in vitro lymphocyte function was impaired and an increase in viral replication occurred after treatment.