Interleukin (IL)-10 may have a role in the treatment of cytokine-associated inflammatory syndromes. The Jarisch-Herxheimer reaction (J-HR), which follows antibiotic treatment of Borrelia recurrentis infection, is a useful model of acute systemic inflammation associated with a cytokine surge and characteristic pathophysiologic changes. In a double-blind, placebo-controlled study, 49 Ethiopian men with B. recurrentis infection were randomized to receive a single intravenous bolus of either 25 microg/kg of recombinant human (rh) IL-10 or vehicle control shortly before receiving intramuscular penicillin. Patients were monitored for physiologic changes, and plasma samples were taken repeatedly for 24 h after treatment. rhIL-10 had no impact on changes in any of the physiologic parameters of J-HR, plasma cytokine levels, or the rate of spirochete clearance. A single intravenous bolus of 25 microgram/kg of rhIL-10 does not seem to have a useful role in the treatment of the J-HR associated with B. recurrentis infection.