The valence ionization potentials of seven additional members of a series of 2,4,5-trisubstituted amphetamines (1-phenyl-2-aminopropanes) were measured by UV photoelectron spectroscopy. These and previously published data provide experimental measures of the gross electron-donor ability of the aromatic rings of 23 amphetamines. Analogues bearing the 2,5-dimethoxy orientation were found to possess the lowest ionization potentials (IPs); for the analogously X-substituted compounds, the IPs increased in the order of 2,5-(OMe)2-4-X less than 2,4-(OMe)2-5-X less than 4,5-(OMe)2-2-X. Relationships between human psychotomimetic activity (MU), rabbit hyperthermia (SRU), serotonergic receptor affinity (pA2), and charge-transfer complex stabilities (KDNB) were evaluated statistically. A good correlation (r2 = 0.92) was established between the human and rabbit potencies, but poorer correlations were obtained between animal potencies and pA2's (r2 = 0.68-0.69) or KDNB's (r2 = 0.03!). Analysis of the regression relationships between these pharmacological measures and two physical properties, IP and lipid solubility (as modeled by log P), were explored. In general, greater potency is associated with decreasing IP and increasing log P. However, numerous exceptions to single parameter regressions are found. The unusually great potency of the 2,5-(OMe)2-4-X analogues, while qualitatively related to the physical properties, is quantitatively underestimated by these predictors. However, inclusion of a parameter (pi 4) which explicitly acknowledges the type of the 4-substituent leads to much improved correlations. These results support previous suggestions that 4-substituents interact directly with the receptor.