Sunscreen use can reduce the incidence of certain skin cancers. However, a number of commercially available formulations have been shown to enhance the transdermal penetration of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Most of the active ingredients used in these compounds can individually act as penetration enhancers. Commercial sunscreens frequently contain multiple active ingredients in order to provide broad sunscreen protection. The purpose of this study was therefore to examine the effect of these active ingredient combinations on the transdermal absorption of 2,4-D in vitro. All six of the combinations tested resulted in increased cumulative penetration ( P <0.01) and faster lag times ( P <0.05). The 2,4-D cumulative penetration in the presence of the OFF! Deepwoods combination was significantly greater than the absorption with either the individual ingredients or their average ( P <0.05). A systematic study designed to isolate the chemicals responsible for this enhancement demonstrated that with UV absorbers DEET synergistically increased the 2,4-D penetration and that DEET’s cumulative enhancement properties correlate with its concentration. By contrast, octocrylene significantly slowed the lag time when used in combinations and was the only active ingredient that showed any antagonistic effects on 2,4-D penetration. Because none of the active ingredient combinations were able to inhibit dermal uptake of 2,4-D, it seems that proper selection of inert ingredients may be the most feasible solution for reducing penetration enhancement.