Topical therapy with 2.5% calcium gluconate gel is considered as the "first-aid" treatment of accidental hydrofluoric acid skin burns. The efficacy of three different gel formulations varying in the amount and/or nature of their gelling and moisturizing agents was experimentally evaluated. Thirty male Wistar-Han rats (250 g) were exposed to 60 mul of 40% hydrofluoric acid for 2 minutes on two spots (4 cm) of skin under pentobarbital anesthesia. One lesion was massaged with 1 g of gel (10 rats/type of gel) at 3 minutes; 30 minutes; 1 hour; 1 hour, 30 minutes; 2 hours; 3 hours; and 4 hours after injury. During the next 3 days, rats received a single daily application of gel. The other lesion for each rat remained untreated (control). From day 1 after injury to the end of the study (day 17), gel therapy reduced the number of extensive (-66%), severe (-44%), and moderate (-34%) lesions (P < .0001). It reduced (P < .001) the median Area Under the Curve day 0-17 of burn injury from 34.0 (25th to 75th percentile: 18.2-44.5; untreated lesions) to 17.7 (7.0-26.7); overall, there was three cases of treatment failure. At day 17, full wound recovery was obtained in 14 cases by gel therapy compared with 6 in the absence of treatment. The efficacy of the three gel formulations was comparable for all evaluated parameters. Repeated applications of a 2.5% calcium gluconate gel is an efficient treatment of experimental 40% hydrofluoric acid skin burn; few differences were observed between evaluated gel formulations.