We performed a randomized, double-blind, placebo-controlled trial to assess the tolerance and efficacy of recombinant human interferon alpha 2a (Roferon A) in patients with acquired immunodeficiency syndrome (AIDS) without Kaposi's sarcoma. A total of 67 patients were enrolled in five medical centers from October 1983 through April 1986, and received either placebo, 3 million units, or 36 million units of interferon alpha three times a week for 12 weeks. There were no significant differences in median survival, frequency of development of opportunistic infections, median T4-cell counts, or serum p24 antigen levels during therapy among the three groups. There was a significant increase in weight in the 3-million-unit group compared with 36-million-unit and placebo groups. Adverse reactions were common in the two interferon groups, but did not differ significantly from the placebo group. Neither significant therapeutic benefit nor adverse reaction was demonstrated in this study to be associated with interferon-alpha administration. This study underlines the value of randomized, double-blind, placebo-controlled studies to address specific issues of drug efficacy and toxicity.