Studies to determine the extent of local tissue penetration of topically applied, commercially available salicylate esters and salts were conducted in male Wistar rats. The salicylate concentration in plasma, tissues underlying the site of drug application, and similar tissues on the contralateral (control) side were measured. The plasma and tissue salicylate levels suggest that direct penetration of salicylate was predominant to the top muscle level on the treated site. Results also suggest that the drugs were first absorbed into the bloodstream and subsequently distributed to both the deeper tissues on the treated site and the contralateral tissues. The topical application of formulations of ester methyl salicylate and salts triethanolamine salicylate and diethylamine salicylate containing comparable salicylate concentrations yielded similar salicylate concentrations in the various tissues. The salicylate concentrations in the deeper tissues approached concentrations observed in the contralateral tissues suggesting that salicylate present in these tissues was due to the systemic blood supply.