A clinical trial of the combination of trimethoprim and sulfamethoxazole (TMPSMZ), was conducted in 86 patients with brucellosis, hospitalized either in Trikala (Thessaly) or in Athens. All cases had the typical clinical picture of acute brucellosis, or that of special localizations and high titers of agglutination reactions in their sera. In 39 patients the diagnosis was confirmed by positive blood cultures. There were 14 cases of osteoarthritic localization, one severe case of brucella endocarditis, and two cases of epididymo-orchitis. Clinical response to the drug was good in 78 cases, with defervescence ensuing within two to eight days. In eight cases the response was not satisfactory. Relapses occurred in 4% of all cases. Bacteriologic response was observed in 19 of 39 patients. In 15 patients the blood ;culture remained positive although the clinical response was good. There were five patients who initially had a negative blood culture, and later a positive culture. Dosage varied from four to six tablets, occasionally eight tablets daily. Duration of treatment was generally one month at first, and subsequently two months. It is concluded that TMP-SMZ is effective in the treatment of acute brucellosis and in some special forms such as osteomyelitis and endocarditis. Longer duration of treatment and the higher initial doses seem warranted to improve results and prevent recurrences.