The safety of continuous i.v. interleukin-2 (IL-2) in conjunction with zidovudine (ZDV) was assessed in asymptomatic patients infected with human immunodeficiency virus. Clinical, immunologic, and viral parameters were monitored in a phase I/II trial with dose escalation and crossover arms. Daily doses of IL-2 from 1.5 to 12 x 10(6) IU/m2 were well tolerated and, in the presence of ZDV, did not induce increases in p24 antigenemia. Significant (p less than 0.05) but transient increases in CD4 cells were observed midway through infusion of IL-2 at all doses, and increases in natural and lymphokine-activated killer activity were seen at higher doses. Circulating hypodense eosinophils and soluble IL-2 receptors increased more than 10-fold. Of nine patients available for long-term follow up 13-25 months from baseline and 4-21 months after stopping IL-2, six still had improved CD4 counts (versus baseline), and the mean increase (135/mm3) for all nine patients was significant (p less than 0.05). Eight of these nine patients were negative for serum p24 at the start of therapy, and none had become p24 antigenemic at long-term follow-up.