Single-dose non-random, antibiotic treatment was evaluated in 377 Ethiopians with louse-borne relapsing fever. Oral doses of tetracycline hydrochloride 500 mg, doxycycline 100 mg, erythromycin base 500 mg, chloramphenicol 500 mg, or a single intramuscular injection of 1,200,000 units of penicillin aluminum monostearate (PAM) were equally effective treatments. All drugs induced a Jarisch-Herxheimer reaction, which was clinically less severe in patients given PAM. The duration of spirochetemia after treatment was much longer after PAM treatment, however. Three critically ill patients died shortly after receiving antibiotic treatment, from complications of LBRF that were present on admission to hospital.