A multicenter, randomized, evaluator-blinded, placebo-controlled clinical study was conducted to evaluate the safety and effectiveness of glycyl-l-histidyl-l-lysine: copper complex (lamin Gel) in the treatment of diabetic neuropathic ulcers. All patients were enrolled in an aggressive standardized wound care protocol consisting of sharp debridement at study entry, daily application of a metered dose of drug, standardized pressure-relieving footwear, and patient education relating to diabetes control and activity modifications. Treatment with lamin Gel significantly increased the percentage of closure of plantar ulcers (98.5% median area percentage closure compared with 60.8% for vehicle; p < 0.05) and the proportion of patients healing 98% or better. The rate of closure was three times faster with lamin Gel treatment compared with standard care and vehicle. The enhancement of wound closure was more pronounced (median of 89.2% compared with -10.3% for vehicle; p < 0.01) in larger (greater than 100 mm(2) initial area at study entry) plantar ulcers caused by the failure of this size of ulcer to respond adequately to standardized wound care treatments in the absence of lamin Gel. Treatment must commence immediately after the initial wound debridement to obtain optimal enhancement of the ulcer closure. The incidence of ulcer infections was significantly lower (7% incidence compared with 34% for vehicle, p < 0.05) in the plantar ulcers treated immediately after debridement with the lamin Gel.