The analgesic effects of intradermal lidocaine infiltration and topical EMLA cream applications (eutectic mixture of local anaesthetics) were studied in 8 patients with Ehlers Danlos syndrome type III, a heritable disorder of connective tissue, and in 8 controls. Cutaneous analgesia was evaluated by sensory and pain thresholds to short argon laser stimulation, and the depth of cutaneous analgesia was measured by sensory and pain thresholds to controlled needle insertion. Five minutes after lidocaine infiltration, the laser-induced pain was abolished in both groups, but 1 h later only the skin of the controls remained analgesic. EMLA cream was applied for 30, 60, and 120 min, but none of the patients obtained sufficient analgesia. Full analgesia was obtained for the controls after 60 and 120 min of application. The depth of cutaneous EMLA analgesia was significantly less for the patients compared to controls. The present quantitative findings support clinical observations that long-lasting cutaneous analgesia is difficult to obtain for this group of patients.