An outbreak of low pathogenic avian influenza (LPAI) subtype H6N1 (intravenous pathogenicity index = 0.11) infection occurred in four productive brown layer flocks on three farms in the Netherlands within a period of two months. The farms were located at a maximum distance of 4.6 km from each other. The infections were associated with egg production drops up to 74%, pale eggshells and persisting high mortality up to 3.2% per week. Three flocks were slaughtered prematurely as they were not profitable anymore. Newcastle disease, infectious bronchitis, egg drop syndrome and Mycoplasma gallisepticum infections could very likely be excluded as cause of or contributor to the condition in the field. Also, the anticoccidial drug nicarbazin, which can cause egg production drops and eggshell decolouration, was not detected in eggs from affected flocks. Furthermore, post mortem examinations revealed no lesions indicative of bacterial infection. Moreover, bacteriological analysis of hens was negative. The condition was reproduced in commercial brown layers after intratracheal inoculation with virus isolates from affected flocks. It is concluded that the LPAI H6N1 virus is very likely the only cause of the disease. An overview of main manuscripts published since 1976 describing non-H5 and non-H7 avian influenza (AI) virus infections in chickens and their biological significance is included in the present study, in which once more is shown that not only high pathogenic AI virus subtypes H5 and H7 can be detrimental to flocks of productive layers, but also non-H5 and non-H7 LPAI viruses (H6N1 virus). RESEARCH HIGHLIGHTS LPAI H6N1 can be detrimental to productive layers Detrimental effects are severe egg drop and persistent high mortality LPAI H6N1 virus outbreak seems to be self-limiting.