Cellular responses induced in two Creole goats by vaccination with killed Cowdria ruminantium (Cowdria) were confirmed by IFN-gamma production and interleukin-2 receptor (IL-2R) expression. Both CD4+ and CD8+ but not WC1+ T cells showed a substantial increase in cell surface expression of IL-2R molecules in response to whole Cowdria lysate. Cowdria (Welgevonden strain) proteins were fractionated using continuous-flow electrophoresis and tested for their ability to induce IFN-gamma production by PBMC collected three weeks after the first inoculation and one week after the booster injection. Pooled fractions of around 15, 22, and 24 kDa were found to induce significant IFN-gamma production in both vaccinated animals on one of the two occasions. Antigens of around 15 kDa induced substantially higher IFN-gamma production than any other fractions in both animals. These pilot experiments pave the way towards the identification of proteins/genes that have potential for the development of a recombinant vaccine against heartwater.