Proteins involved in intracellular protein folding in bacteria and eukaryotes have now been shown to be secreted and act as intercellular signals. Have focused on the chaperonin 10 and chaperonin 60 proteins of the pathogenic bacterium Mycobacterium tuberculosis and of Homo sapiens. Mycobacterium tuberculosis encodes two chaperoin 60 genes. We have discovered that the Cpn60.1 protein of this organism is not a molecular chaperone but a secreted protein with a potent ability to inhibit the generation on bone-resorbing osteoclasts and induce the formation of multinucleate giant cells. Inactivation of the cpn60.1 gene in M. tuberculosis has no obvious in vitro phenotype but this isogenic mutant, while growing at a similar rate to the wild type or complemented organism, fails to induce granulomatous inflammation in the lung. We have established that the 50-60% of the normal human population has levels of human Cpn60 in their plasma ranging from 1ng/ml to >1mg/ml. This is the greatest range of concentration of any human plasma protein. Levels of this molecular chaperone appear to correlate with susceptibility to coronary artery disease and diabetes.