The aim of this study was to determine whether topical application of diclofenac hydroxyethylpyrrolidine (DHEP) modifies somatic pain sensitivity in subjects without spontaneous pain. Twenty male subjects (aged 19-40 years), who had not reported any pain for at least 1 month, underwent measurement of pain thresholds to bilateral electrical stimulation in the quadriceps muscle and overlying subcutis and skin. Following the double-blind study design, one diclofenac adhesive plaster (13 x 10 cm; 180 mg DHEP) was then applied over one quadriceps while a matched placebo plaster was placed contralaterally. Each subject was given two other plasters (diclofenac and placebo) and instructed to substitute those over the quadriceps after 12 h and to wear them for a further 12 h. Thirty minutes after removal of the second plasters, thresholds. were remeasured in all subjects as on the previous day. Thresholds at the first evaluation were within normal range in nine subjects (group 1) and below normal in muscle (hyperalgesia) in the remaining 11 (group 2). No significant changes were observed in skin or subcutis thresholds after diclofenac or placebo treatment in either group. In contrast, muscle thresholds significantly increased after diclofenac compared with placebo treatment (group 1: p < 0.05; group 2: p < 0.007); the increase was significantly higher in group 2 than in group 1 (p < 0.002). Topical application of diclofenac had a selective hypoalgesic effect on muscles, which was more pronounced in the case of hyperalgesia. These results suggest that the preparation is particularly effective in the treatment of algogenic conditions of deep somatic tissues.