Serum antibodies to a panel of 13 viruses and to Mycoplasma pneumoniae and Chlamydia psittaci were tested in 17 patients with polymyalgia rheumatica (PMR) and in 17 age- and sex-matched controls with osteoarthritis seen in the same rheumatological clinic. Antibodies to adenovirus (ADV) and respiratory syncytial virus (RSV) were significantly more prevalent in PMR. These antibodies were titred in 26 patients with PMR, including those evaluated in the pilot study (17 women, 9 men, mean age 72.5 years), and in 26 controls. 25/26 PMR patients tested positive for antibodies to ADV vs. 12/26 controls (p = 0.0002) and the concentration was higher in patients than in controls (p < 0.01). Antibodies to RSV were present in all PMR patients and in 12/26 controls (p = 0.00005) and their concentration was higher in patients than in controls (p < 0.01). Serial determinations performed in 18 PMR patients showed that the antibody titer did not change significantly. These data suggest that a trivial infection may trigger PMR in elderly people, with ADV and RSV among the possible microorganisms involved.