A 16-year-old girl developed multiple subcutaneous abscesses, osteomyelitis, and severe colitis. On the patient's second admission, a single blood culture - and, subsequently, a specimen of pus-yielded Brucella melitensis biovar 1. A second set of serologic tests, including the rose bengal test, the standard tube agglutination test, the CF test, and Coombs' test, were all negative for Brucella on the patient's second admission and 1 month later. However, a lymphocyte proliferation assay with extracted antigen of Brucella was markedly positive. Thus, this case illustrates that patients with B. melitensis infection may have a unique clinical presentation and that the lymphocyte proliferation assay is an important diagnostic tool for patients whose serologic test results are negative but for whom brucellosis is suspected.