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Two different vaccination protocols were compared with regard to the development of hypertrophic osteodystrophy (HOD) (also termed metaphyseal osteopathy) and effectiveness of immunisation in a litter of 10 Weimaraner puppies. Five puppies (group 1) were vaccinated with a modified live canine parvovirus vaccine (CPV) and then two weeks later with a trivalent vaccine containing modified live canine distemper virus and adenovirus type 2 combined with a Leptospira bacterin (DHL). The CPV and DHL vaccine protocols were administered a further two times, at two-week intervals. Group 2 was vaccinated with three consecutive multivalent vaccines containing modified live canine distemper virus, canine parvovirus, parainfluenza and adenovirus type 2 combined with a Leptospira bacterin, at four-week intervals. All puppies were first vaccinated at the age of eight weeks. Three dogs in group 1 developed HOD, while all five dogs in group 2 developed HOD during the study period. Dogs in group 2 had more episodes of HOD than those in group 1. Dogs in group 1 developed higher antibody titres to canine distemper virus and parvovirus compared with those in group 2. Only two out of the 10 dogs developed protective antibody titres to parvovirus. The results of this study suggest that the two different vaccination protocols affected the pattern of appearance of HOD and immunisation in this litter of Weimaraner puppies. The results obtained and the previously reported data suggest that a larger controlled study is needed to further elucidate the effect of different vaccination protocols on HOD and immunisation in Weimaraner puppies.