The effects of exercise, heat exposure or both on the percutaneous absorption of methyl salicylate were studied in 6 healthy volunteers. Exercise was performed to 30% of VO2max, 45 min each hour for 6 h, at ambient temperatures of 22 degrees C or 40 degrees C. Systemic availability was assessed by measurement of plasma salicylate concentrations and cumulative urinary salicyluric acid excretion over an 8-h collection period. The absorption of methyl salicylate was increased to more than 3-times above control in subjects exercising in the heat. It is concluded that exercise and heat exposure, by increasing skin temperature, hydration and blood flow, enhance the percutaneous absorption of methyl salicylate.