In an open study of the treatment of patients with AIDS-related complex (ARC) and AIDS with zidovudine, we evaluated the response of serum p24 antigen (p24Ag) and antibody to p24Ag (anti-p24) levels. Before treatment, serum from 49 out of 73 (67%) patients was p24Ag-positive, and of these patients 42 received zidovudine 800-1200 mg daily for greater than 4 weeks and had a baseline mean serum level of p24Ag of 119 pg/ml (s.e. 15.7). On zidovudine there was a reduction of p24Ag to 21.12% (s.e. 4.76) of pretreatment values at 3 months; however, there was a subsequent trend for levels after 6 months to increase to greater than 50% of pretreatment levels at 12 months. Serum levels of anti-p24 were measured in 26 patients. Of 16 patients whose serum contained p24Ag and 10 whose serum did not, four and nine, respectively, had detectable levels of anti-p24. There was no significant change in the serum anti-p24 with zidovudine therapy.