The amphiphilic alpha-helical peptide (KIAGKIA)3-NH2 (MSI-103) is a designer-made antibiotic, based on the natural sequence of PGLa from Xenopus laevis. Here, we have characterized the concentration-dependent alignment and dynamic behavior of MSI-103 in lipid membranes by solid-state 2H and 19F NMR, using orientational constraints from seven Ala-d3-labeled analogues and five 4-CF3-phenylglycine labels. As previously found for PGLa, MSI-103, too, assumes a flat surface-bound S-state alignment at low peptide concentrations, and it also realigns to a tilted T-state at higher concentrations. For PGLa, the stability of the T-state had been attributed to the specific assembly of antiparallel dimers; hence, it is remarkable that the artificial KIAGKIA repeat sequence can also dimerize in the same way in liquid crystalline lipid bilayers. Oriented circular dichroism analysis shows that for MSI-103 the threshold for realignment from the S-state to the T-state is approximately 3-fold lower than for PGLa (at a peptide-to-lipid ratio of 1:240 in dimyristoylphosphatidylcholine, compared to 1:80). Furthermore, MSI-103 becomes laterally immobilized in the lipid bilayer at a concentration ratio of 1:50, which occurs for PGLa only above 1:20. The superior antimicrobial activity of MSI-103 over PGLa thus appears to correlate with its stronger tendency to realign and self-assemble. The hemolytic activities of MSI-103 and its analogues, on the other hand, are shown here to correlate purely with the respective changes in hydrophobicity.