A total of 837 healthy volunteers presenting with various degrees of obesity participated in a large-scale, double-blind, placebo-controlled evaluation of the subjective effects of phenylpropanolamine (PPA), with particular attention to measurement of the euphoriant or stimulant potential of therapeutic doses of the compound. Dosage forms studied were PPA 75 mg sustained release, PPA 25 mg, and placebo. Subjects were recruited from four independent clinical sites. At each site, subjects were stratified according to degree of overweight (normal, mildly overweight, moderately overweight, or severely overweight) and randomly assigned to one of the three drug treatment regimens. Subjective effects were measured 11 times during the 12-hour experimental session using a short-form version of the Addiction Research Center Inventory. Data analysis did not indicate discernible subjective effects that would differentiate PPA from placebo, but did show typical circadian fluctuations. These results provided evidence that therapeutic doses of PPA do not produce the euphoriant or "stimulant" subjective effects that characterize drugs of abuse.