Contagious caprine pleuropneumonia (CCPP) is an important caprine disease in Africa and Asia. Mycoplasma capricolum subsp. capripneumoniae (Mccp), the causative agent, is fastidious and grows slowly, which makes vaccine production cumbersome. In low and middle income countries disease control currently depends on a bacterine vaccine. We are developing a live CCPP vaccine that can be combined with other caprine live vaccines such as peste des petits ruminants (PPR), to reduce costs associated with production and vaccination campaigns. The full genome sequence of the recent Kenyan field isolate of Mccp, ILRI181 was determined (1). Strain ILRI181 significantly outcompetes the current type and vaccine strain F38 in terms of its growth characteristics. Moreover, it produces high levels of peroxide in the presence of glycerol and shows cytotoxic activity against transformed goat fibroblast (TGF) cells, a pathogenicity mechanism that has not been shown for Mccp before. We established a novel challenge model for CCPP. Due to low transmission rates of Mycoplasma we opted for a repeated exposure to the pathogen via a combination of two intranasal and one transtracheal infection. We infected 10 goats with 3 x 108 ccu over five days. Two consecutive daily intranasal infections were followed by transtracheal infection on day five. All animals developed clinical disease with fever and six had to be euthanized because of ethical reasons before the envisaged termination of the trial. Post mortem examination revealed classical CCPP lesions characterised by severe fibrinous pleuropneumonia with pleural effusion (6/10), pleural adhesions (10/10), sequestra (3/10) and renal infarcts (1/10). Titrations of lung exudate and pleural fluid resulted in up to 109 Mccp per ml (2). We mutagenized strain ILRI181 using the acridine chemical ICR-191 and are currently screening the mutant library for clones that do not produce peroxide. Next we will test vaccine candidates for attenuation and efficacy.