Etodolac SR is the sustained-release formulation of etodolac, an effective anti-inflammatory drug used in the treatment of various rheumatic diseases. The efficacy and safety of etodolac SR were compared with those of tenoxicam in 120 elderly patients with radiographic and clinical evidence of active osteoarthritis (OA) of the knee and/or the hip. This was a double-blind, double-dummy, randomized, parallel-group, multicentre study conducted at 4 Italian rheumatic-disease units. Sixty patients received 600 mg of etodolac SR once daily (u.i.d.) for 8 weeks; the remaining 60 patients received 20 mg of tenoxicam u.i.d. Significant improvements in all 6 efficacy parameters (viso-analogic scale of the global pain, pain at active movements, night pain, joint tenderness, joint motility, and Lequesne's algofunctional index) were observed within each of the treatment groups even after the first 2 weeks of therapy. There were no significant differences in the therapeutic response between the two groups for any efficacy parameters. Adverse reactions, mostly regarding the G-I tract, were significantly more frequent in the tenoxicam group than in the etodolac group: 23.3% vs 8.3% respectively, albeit in the majority of the cases they were not considered to be so severe as to cause the interruption of the study. There were no clinically important changes from baseline in laboratory tests performed during the study. Endoscopy of the upper G-I tract was performed both at baseline and after 8 weeks of therapy in 30 patients per treatment group in order to obtain a reliable comparative evaluation of the G-I safety of the two drugs. Both drugs were found to be well tolerated; only 2 ulcers were observed after therapy in both groups, but minor lesions were more frequently detected in the mucosa of the stomach in the patients who received tenoxicam. The cumulative endoscopic index that reflected both the erosive and the haemorrhagic lesions found in the stomach taken as a whole was significantly (p < 0.03) higher after therapy in the tenoxicam group. These results indicate that 600 mg of etodolac SR u.i.d. for 8 weeks is as effective as 20 mg of tenoxicam u.i.d. in the treatment of OA of the knee and/or of the hip. Both the overall and the G-I specific safety profiles were found to be more favourable in patients treated with etodolac SR. Renal function was not substantially affected in either treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)