During human Coxiella burnetii (C. burnetii) infections, high IL-10 levels favor replication of C. burnetii in monocytes and development of chronic Q fever, whereas IFN-gamma promotes intracellular killing. Sheep are a common source for human C. burnetii infections, but in contrast to man become transiently infected only. In a first approach to unravel the role of cytokines during ovine C. burnetii infections, we investigated by semiquantitative RT-PCR whether heat-inactivated C. burnetii affects the transcription of genes coding for IL-2, IL-4, IL-10, and INF-gamma in vitro in PBMC from sheep seropositive or seronegative for C. burnetii. By computer-assisted evaluation of band intensities the transcription rate of the cytokine genes was quantified in relation to transcription in Concanavalin A-stimulated and nonstimulated controls. Transcription rates in PBMC from seropositive animals after incubation with C. burnetii for 4 hours strongly resembled those found in PBMC from seronegative sheep. However, upon prolonged incubation (24 h) C. burnetii induced an increased IL-10 transcription in PBMC from 2 of 5 seronegative, but in PBMC from 5 of 5 seropositive animals. The data suggest that natural C. burnetii infections prime the ovine immune system towards a T(H)2-like pattern and this action thereby represents the first clue for the involvement of ovine immune cells in the response to C. burnetii infections.