Human serum amyloid A (SAA) is a precursor protein involved in AA amyloidosis. The N-terminal region of the SAA molecule is crucial for amyloid fibril formation, and therefore modifications in this region are considered to influence the pathogenesis of AA amyloidosis. In the present study, using the N-terminal peptide corresponding to the putative first helix region of the SAA molecule, we investigated the influences of N-terminal modifications on amyloid fibril formation. Spectroscopic analyses revealed that carbamoylation of the N-terminal amino group delayed the onset of amyloid fibril formation. From transmission electron microscopic observations, the N-terminal carbamoylated aggregate showed remarkably different morphologies from the unmodified control. In contrast, acetylation of the N-terminal amino group or truncation of N-terminal amino acid(s) considerably diminished amyloidogenic properties. Furthermore, we also tested the cell toxicity of each peptide aggregate on cultured cells by two cytotoxic assays. Irrespective of carbamoylation or acetylation, MTT assay revealed that SAA peptides reduced the reductive activity of MTT on cells, whereas no apparent increase in LDH release was observed during an LDH assay. In contrast, N-terminal truncation did not affect either MTT reduction or LDH release. These results suggest that N-terminal modification of SAA molecules can act as a switch to regulate susceptibility to AA amyloidosis.