Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized, multicenter trial, a rising single dose of SCH55700 (0.03 mg/kg [n = 2], 0.1 mg/kg [n = 4], 0.3 mg/kg [n = 6], or 1.0 mg/kg [n = 12]) or placebo (n = 8) was administered intravenously. SCH55700 dose dependently reduced circulating eosinophil counts. At a dose of 1.0 mg/kg, the decrease remained significant up to Day 30 [(0.07 +/- 0.01) x 10(9)/L versus (0.23 +/- 0.04) x 10(9)/L at baseline] (mean +/- SEM) (p = 0.05). After administration of SCH55700 at 0.3 and 1.0 mg/kg, a trend toward improvement in baseline FEV1 was observed, which reached significance 24 hours after the 0.3-mg/kg dose (p = 0.019 versus placebo). No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo. We conclude that SCH55700 is a biologically active anti-human IL-5 antibody that can be safely used in severe steroid-treated asthma. Its therapeutic potential needs to be addressed in specifically designed efficacy trials.