In thermal resort of Garniga in Bondone Alp, Trento (Italy), spa therapy of osteoarthritis is carried out with applications on body of fermenting grass from Bondone prairies, 1600 m above sea-level. During application heat is developed and grass compounds are released. The mechanism of therapy is not well known. Heat shock proteins 70 (Hsp 70) and 60 (Hsp 60) were determined in serum of fifteen patients with knee joint osteoarthritis treated with standard therapy (11 applications in 2 weeks). Clinical assessments were carried out and serum was collected before and after the third and the ninth application and after one, three and six months. Hsps 70 and 60, were determined by immunoassay.Funtional impairment (Lequesne’s index), pain rating, quality of life indexes, analgesic and/or NSAID consumption significantly improve after treatment up to the end of the follow-up period. Improvement of physical activity and of psychic and physical wellbeing is also obtained. Significant increasing of Hsp 70 level is observed after the third application with a maximum after the 9th application then decreases progressively. No variations of Hsp 60 serum level are found. No adverse reactions were reported.Conclusion. Heat produced by grass applications determines a controlled repeated heat shock which increases extra-cellular and probably intracellular Hsp 70 at joint level increasing cellular defences and modulating local and general immunity responses. Possible roles of grass-released compounds remain to be investigated.