Clinical signs and gross lesions observed in poultry submitted for postmortem examination (PME) from the first five infected poultry flocks preceding the detection of the primary outbreak of highly pathogenic avian influenza (HPAI) of subtype H7N7 during the 2003 epidemic in the Netherlands are described. The absence of HPAI from the Netherlands for more than 75 yr created a situation in which poultry farmers and veterinary practitioners did not think of AI in the differential diagnosis as a possible cause of the clinical problems seen. Increased and progressive mortality was not reported to the governmental authorities by farmers or veterinary practitioners. It took 4 days from the first entry of postmortem material to notify the governmental authorities of a strong suspicion of an AI outbreak on the basis of a positive immunofluoresence test result. The gross lesions observed at PME did not comply with the descriptions in literature, especially the lack of hemorrhagic changes in tissues, and the lack of edema and cyanosis in comb and wattles is noted. The following lessons are learned from this epidemic: a) in the future, increased and progressive mortality should be a signal to exclude AI as cause of disease problems on poultry farms; b) intensive contact between the veterinary practitioner in the field and the veterinarian executing PME is necessary to have all relevant data and developments at one's disposal to come to a conclusive diagnosis; c) in an anamnesis, reporting of high or increased mortality should be quantified in the future (number of dead birds in relation to the number of birds brought to the farm to start production, together with the timing within the production cycle), or else this mortality cannot be interpreted properly; d) if clinical findings such as high mortality indicate the possibility of HPAI, the pathologist should submit clinical samples to the reference laboratory, even if PME gives no specific indications for HPAI; e) the best way to facilitate early detection of an HPAI outbreak is to have the poultry farmer and/or veterinary practitioner immediately report to the syndrome-reporting system currently in operation the occurrence of high mortality, a large decrease in feed or water intake, or a considerable drop in egg production; f) in order to detect low pathogenic avian influenza infections that could possibly change to HPAI, a continuous serologic monitoring system has been set up, in which commercial poultry flocks are screened for antibodies against AI virus of subtypes H5 and H7.