Serpin peptides modify cell activation as measured by membrane fluidity in vitro. Membrane fluidity assays measured as Iex/Imon fluorescence of BPP-labeled THP-1 monocytes demonstrated increased Iex/Imon ratios with PMA activation. Peptide treatments paralleled in vivo activity with the one exception being the S-4 peptide. The S-6 peptide, which caused excess thrombosis, displayed inhibitory activity for cells. Serp-1 peptides S-1 (A), S-3 (C), and S-7 (G) and NSP peptides S-4 (D), S-6 (F), and S-8 (H) significantly reduced membrane fluidity in PMA-activated THP-1 monocytes. Serp-1 peptide S-5 (E) and NSP peptide S-2 did not reduce membrane fluidity in PMA-activated THP-1 monocytes. Serp-1 and NSP consistently reduced membrane fluidity significantly. Error bars, S.E.