This research explored whether in vitro release and skin permeation tests, combined with in vitro and in vivo stratum corneum (SC) sampling, can quantify the "input rate" of a volatile drug into and through the skin. Two topical methyl salicylate (MeSA) products were studied. Drug release from the formulations across a silicone membrane was similar, with ~ 65% of the drug load being released in 6 h. In vitro porcine skin permeation tests showed that ~ 50% of the dose crossed the skin in 24 h from both products. In SC sampling experiments, the mass of MeSA in the SC at one 'uptake' and three 'clearance' time points was measured in vitro and in vivo (in humans). The MeSA quantity taken up into the SC in vitro was > 10-fold higher than that in vivo. The first-order rate constants describing clearance from the SC were calculated and found to be similar, in vitro and in vivo, for both formulations. Mass balance revealed that about one-third of the applied drug may have been lost by evaporation in vitro from the skin surface during 2 h of clearance. The results show that the cutaneous pharmacokinetics of MeSA are proportional to the amount of drug in the two formulations and that the complementary use of in vitro release and skin penetration tests with the SC sampling technique are valid tools with which to assess topical products containing volatile drugs.