The arrival of Katsuhiko Tatemoto in Viktor Mutt's group at Karolinska Institutet (KI), as a PhD student, turned out to be the start of a new and very successful era of this already famous peptide laboratory. With an enormous energy and skill Kei, as he was called first by Viktor and then by everybody else, took on his project. At the basis was a genial technical innovation – the idea to search for peptides, in extracts stored in Viktor's freezers, not by purification and subsequent bioassay, but purely based on chemistry: Screening for amidation sites. In Tatemoto's thesis, including three Nature and one PNAS paper, perhaps one of the most important PhD theses at KI, he described the discovery of four new peptides, PHI, PYY, PPY and NPY, and briefly after that, but not included in the thesis, galanin. These peptides were rapidly made available to us at KI and also to many other laboratories around the world, for example to Drs. Bloom and Julia Polak in the UK. Thus a wealth of interesting data were rapidly generated, not only concerning levels and distribution, but also the function of these peptides. Our own work has focused on NPY, but even more so on galanin. To attempt to make this symposium focused we have decided to disregard our galanin studies. Instead we report on a role of NPY (plus AGRP and some other peptides) in food-intake control, but in a very special animal model – the 'anorectic' (anx/anx) mouse. This mouse dies 3–4 weeks after birth due to a markedly reduced food intake and was first described in 1984 in a report from the Jackson Laboratory. Its phenotype is due to a spontaneous mutation that has been target of our work but still has not been identified. Thus this presentation focuses on anorexia, a serious but much less common eating problem than obesity. Our results show a very distinct phenotype of hypothalamic arcuate cells and their projections in the anx/anx mouse: (1) upregulation of orexigenic NPY and AGRP in the arcuate neuronal cell bodies, but an apparent loss of these peptides in the terminal ramifications, (2) neurodegenerative changes in the AGRP and adjacent POMC neurons, and (3) evidence for inflammatory processes. The search for the mutation has progressed, and at present our candidate gene is Nudfaf1, an assembly factor for the 47 or so proteins of complex I in mitochondria. This is associated with decreased levels of fully assembled complex I and increased oxidative stress, which may contribute to the degenerative changes observed. The putative mutation should affect all cells, but we hypothesize that the reason for the apparently fairly selective involvement of the arcuate NPY/AGRP and POMC neurons is that this food intake-controlling system is very active in the early postnatal period and thus sensitive to energy deficiency. Our results provide further evidence for an important role of one of the neuropeptides, NPY, discovered by Kei Tatemoto and Viktor Mutt.