The purpose of this study was to compare and evaluate two different regimens of treatment in brucellosis. Two hundred and eighteen patients (183 women, 97 men, 16 years to 85 years of age) diagnosed as brucellosis on the basis of both clinical and serologic findings were included in the study. The patients were evaluated as to clinical signs, laboratory findings and outcome of antimicrobial therapy. The predominant presenting symptoms and signs were fever, malaise, night sweats, arthralgia, hepatosp/enomegaly and lymphadenopathy. The patients were divided into two groups: Ninety patients (first group) received tetracyline, 500 mg every 6 hours for 45 days plus streptomycin 1 g/day for 21 days. One hundred and ninty patients (second group) received doxycycline 100 mg every 12 hours plus rifampin 600 mg/day for 45 days. The relapse rate in five months of follow-up was 12.5% in the first group and 14.7% in the second group. There were no statistically difference between the groups. There was sacroileitis in 30% of the relapsing patients in the first group and 74.5 % of the relapsing in the second group. There was statistically a significant difference between the two groups (p< 0.05). Relapsing patients were given doxycycline 100 mg every 12 hours, and rifampin 600-900 mg/day for 6 weeks plus streptomycin 1 g/day for three weeks. Doxycycline-rifampin combination therapy for 45 days was as effective as the classic tetracycline and streptomycin combination in most patients with brucellosis; however, doxycycline and rifampin therapy might be less effective in those patients with spondylitis. Thus patients with spondylitis should be given streptomycine plus rifampin and doxycycline.