In the last few years, there has been continued concern about synthetic drug abuse in both the United States and worldwide. Small adjustments in drug compound structure often allow synthetic drug makers to manufacture a legal product that can produce the same highs as illegal counterparts. Unfortunately, this is happening faster than the government can outlaw the drug compounds, and a wide variety of synthetics are now appearing on the street. This study evaluated the effects on the human serotonin transporter of six different 4-para substituted methcathinone compounds. Using a Xenopus oocyte model, the efficacy of each MCAT analogue at hSERT was calculated by applying the Hill equation to the oocyte data. This study suggests that volume, size, and steric bulk of the compound may generally influence efficacy at hSERT in a direct manner, but that other factors, like lipophilicity, may also play an important role in potency at the transporter.