In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex-and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1␤ (IL-1␤), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzymelinked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-␥, IL-2, and TNF-␣, but not that of IL-4, by phorbol myristate-activated CD4 ؉ CD3 ؉ and CD8 ؉ CD3 ؉ T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-␥ levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.Brucellosis is a zoonotic disease of worldwide distribution. Despite its control in many countries, it remains endemic in the Mediterranean and Middle Eastern regions (20,28,41,42). Brucella melitensis is the most frequent cause of human brucellosis in these geographical areas (19). In Spain, it has been reported that the majority (more than 97.5%) of isolates were identified as Brucella melitensis (13,44,45).Brucella organisms are facultatively intracellular Gram-negative coccobacilli that reside and replicate in a vacuolar compartment within myelomonocytic cells of the infected host (14,15,47). The response to Brucella involves the whole gamut of the immune system, from innate to adaptive immunity (21). In murine models, passive transfer of immune cells resulted in an effective antiBrucella defensive response mediated by CD4 ϩ and CD8 ϩ T lymphocytes (5, 6, 32, 37, 51, 52). Furthermore, the pattern of T-lymphocyte cytokine secretion is considered to be critical for the effectiveness of the protective anti-Brucella immune response (3, 7). It has been postulated that Th1 cytokines confer resistance, while Th2 cytokines facilitate the development of brucellosis (2,3,24,25,40,43,52). In animal models, gamma interferon (IFN-␥) induces macrophage activation and control of Brucella infection (16,18,43). In Brucella-infected mice, administration of recombinant IFN-␥ enhances host resistance, resulting in a deep decrease in the number of viable bacteria (51). Moreover, host IFN-␥ de...