We conducted a double-blind. randomized phase II study to evaluate the safety and activity of combination therapy with N-deoxynojirimycin (SC-48334)(an α-glucosidase I inhibitor) and zidovndine versus zidovudine alone. Patients with 200 to 500 Cl) 4 cells mm 3 who tolerated− 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58. zidovudine and placebo. Twenty-three patients (38%) and 15 (26%). in the combination and zidovudine groups, respectively. discontinued therapy (p-0.15). The mean SC-48334 steady-state trough level (4.04±0.99 μ. g ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells mm 3 and 52.4 cells mm 3 for the combination and zidovudine groups, respectively (p-0.36). lor patients with prior zidovudine therapy. the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells mm 3 and 4.9 cells mm 3 at week 8 and 6.8 cells mm 3 and 45.1 cells mm 3 at week 16. respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p-0.10) and five (45%) and two (14%) at week 24 (p-0.08). respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients. Although superiority of combination therapy was not seen, these data suggest that SC-48334 has anti-HIV activity and provide a rationale for the evaluation of better tolerated compounds of this class.