A study was carried out in five children with acquired immune deficiency syndrome to assess the effect of combined zidovudine/interferon-alpha 2a therapy with that of zidovudine given alone on immunological profiles and plasma zidovudine concentrations. Immunoglobulins A, G and M, total and absolute CD4 lymphocyte counts, and p24 antigen concentrations did not differ significantly when children were treated with 300 mg/m2 zidovudine given orally once every 12 h, or with 150 mg/m2 zidovudine plus 1.5 or 3 MIU interferon-alpha 2a given intramuscularly three times weekly. Peak plasma zidovudine concentrations were significantly (P less than 0.05) lower when combined treatment with 150 mg/m2 zidovudine/1.5 MIU interferon-alpha 2a was administered compared with 300 mg/m2 zidovudine alone, or combined 150 mg/m2 zidovudine/3 MIU interferon-alpha 2a. The results suggest that combination zidovudine/interferon-alpha 2a therapy may be more efficacious than zidovudine alone and that the normal zidovudine dose may be reduced if interferon-alpha 2a is given in addition, thus reducing the side-effects associated with zidovudine.