Targeting the initial formation of amyloid assemblies is a preferred approach to therapeutic intervention in amyloidoses, which include such diseases as Alzheimers, Parkinsons, Huntingtons, etc., as the early-stage, oligomers that form before the development of β-conformation-rich fibers are thought to be toxic. X-ray patterns from amyloid assemblies always show two common intensity maxima: one at 4.7 Å corresponding to the hydrogen-bonding spacing between the β-chains, and the other at ∼10 Å corresponding to the spacing between β-pleated sheets. We report here the application of fiber x-ray diffraction to monitor these structural indicators of amyloid fiber assembly in the presence of small, aromatic molecules, some of which have been assessed by other techniques as being inhibitory. The compounds included butylated hydroxytoluene, chloramphenicol, cotinine, curcumin, diphenylalanine (FF), ethyl 3-aminobenzoate methane sulfonate, hexachlorophene, melatonin, methylpyrrolidine, morin, nicotine, phenolphthalaine, PTI-00703® (Cats claw), pyridine, quinine, sulfadiazine, tannic acid, tetracaine, tetrachlorosalicylanilide, and tetracycline. Their effects on the aggregation of Aβ1-40, Aβ11-25, Aβ12-28, Aβ17-28, Aβ16-22, and Aβ16-22[methylated] analogues were characterized in terms of the integral widths and integrated intensities of the two characteristic reflections. Peptide Aβ11-25 with or without small molecules showed varying relative intensities but similar coherent lengths of 28 – 49 Å in the intersheet and 171 – 221 Å in the H-bonding directions. PTI-00703®, however, abolished the H-bonding reflection. Among previously reported aromatic inhibitors for Aβ11-25, PTI-00703®, tannic acid, and quinine were more effective than curcumin, morin, and melatonin based on the criterion of crystallite volume. For the N-methylated and control samples, there were no substantial differences in spacings and coherent lengths; however, the relative volumes of the β- crystallites, which were calculated from the magnitude of the intensities, decreased with increase in concentration of Aβ16-22Me. This may be accounted for by the binding of Aβ16-22Me to the monomer or preamyloid oligomer of Aβ16- 22. The fiber diffraction approach, which can help to specify whether an amyloidophilic compound acts by impeding hydrogen- bonding or by altering intersheet interactions, may help provide a rationale basis for the development of other therapeutic reagents.