The aim of the study was to assess the effect of maximal therapeutic dosing of sympathomimetic amines found in over-the-counter (OTC) decongestant preparations on endurance running. Following familiarisation and a graded exercise test to determine maximal oxygen uptake (VO2 max), trained male runners (n = 8) completed four exercise sessions each separated by a minimum of one week. Each session was comprised of 20 min of sub-maximal treadmill running (70 % VO2 max) followed by a 5,000-m time trial on the treadmill under drug, placebo or control conditions. Drugs were administered in their commercial format over the 36-hour period prior to testing in the manufacturer's recommended maximal doses (i. e. 25 mg of phenylpropanolamine and 60 mg of pseudoephedrine four times daily). During sub-maximal endurance running no statistical differences were observed in heart rate, VO2, minute ventilation, respiratory exchange ratio, blood lactate, glucose or non-esterified fatty acids (NEFA) or ratings of perceived exertion with respect to the treatment administered. Similarly there were no statistical differences according to the condition during the 5,000-m running time trial, in terms of heart rate, ratings of perceived exertion, time of completion and pre and post exercise blood lactate, glucose or NEFA. The results indicate that in maximal, multiple therapeutic doses both pseudoephedrine or phenylpropanolamine as present in common OTC decongestant formulations do not affect, nor possess any ergogenic properties with regard to, endurance running.