The efficacy of zidovudine (AZT) for treatment of patients with Kaposi's sarcoma as the initial manifestations of AIDS was determined in a non-randomized, phase-II clinical trial. Twenty-two patients were treated with zidovudine (300 mg 4 times daily for 8 weeks). In patients with stable disease or showing a response, treatment was continued. After 12 weeks the total daily dose was changed to 1000 mg. Only two of all 22 evaluable patients achieved a response (one complete and one partial response), of only brief duration (2 and 4 months, respectively). There was no such association between antiretroviral activity, increase in CD4+ cells and tumour response, as was reported during treatment with human recombinant interferon alpha (IFN-α). These findings do not support the use of zidovudine as a first-line treatment for patients with AIDS-associated Kaposi's sarcoma.