A double-blind, placebo (PBO)-controlled trial was carried out on 155 adult outpatients with painful (Huskisson's analogical scale > 40 mm) monolbilateral femorotibial and/or femoropatellar osteoarthritis of the knee, radiologically confirmed. Patients were randomly given either diclofenac hydroxyethylpyrrolidine plasters (DHEP, 78 patients), containing 180 mg of active drug each, or matched PBO (77 ptns). Plasters were applied b.i.d. (at 8 a.m. and 8 p.m.) on the affected joint, for 15 days. No NSAID treatment was allowed during the trial, while paracetamol was admitted from the 4th day on and its daily intake carefully recorded. Huskisson's test and Lequesne's index were assessed at days 0, 4, 7 and 15. Patients were asked to fill in a daily cared with Huskisson's scale and subjective evaluations. Differences in favour of DHEP were observed from the first assessment (4th d.) on Huskisson's scale and Lequesne's index (p < 0.001). According to the patients' subjective evaluation, pain decreased as soon as the first day in both groups, with significant differences in favour of DHEP (p < 0.005). Even the number of night awakenings recorded by the patient was significantly in favour of DHEP (p < 0.005). It is worth noting that these results were obtained in spite of a significant reduction of paracetamol intake in DHEP patients in comparison with PBO patients (p < 0.01). Tolerability was judged good or excellent in the majority of cases: only minor side effects occurred in five patients (4 PBO, 1 DHEP) and the interruption of treatment was required for only one of the PBOs. This study shows that DHEP plaster significantly differs from matched PBO in the improvement of pain and patient's condition in painful knee osteoarthritis.