Immune response of birds reared under different housing systems and vaccinated against avian influenza (AI) was studied using 10 layer and 3 broiler-breeder flocks reared in either deep litter or cage systems. Blood samples were collected at intervals during rearing period and different production periods (start, peak and end of production), and haemagglutination inhibition test (HI) was carried out for all serum samples to determine antibody titers. All Birds reared in deep litter system recorded lower mean HI titers; (6.52 to 8.20 in layers, and 1.53 to 5.31 in breeders) than those reared in cages (8.69 to 10.38 in layers, and 3.27 to 8.83 in breeders). However higher CV% were recorded in birds on deep litter (17.42 to 27% in layers, and 33.09 to 136.58% in breeders) than those in cages (7.90 to 8.84% in layers, and 10.16 to 81.25% in breeders). During peak egg production all birds showed lower titers (6.52 and 10.12), with broiler-breeders showed the lowest titers (4.30 and 3.84). On the other hand, the effect of the route of vaccination (I/M vs S/C) in broiler-breeders was also evaluated and results revealed that I/M vaccination induced better immune response (7.28) and more uniform titers (lower CV % = 23.19%) than S/C route (3.86, 67.87%). These results indicated that cage system provided better environment that enhanced the immune response of birds than those reared in deep litter system. However, the period of peak egg production could be considered as stress factor that reduce immune response, On the other hand, variation between I/M and S/C injection could be due to ill-trained vaccination teams in Egypt; who were more experienced with I/M administration of vaccines and antibiotics rather than the use of S/C route. It was concluded from this study that immune response of vaccinated poultry could be influenced by the type of housing provided for birds and also signifies the importance of the experience of team responsible for vaccine administration in order to achieve the best protective and homogenous antibody titers in broiler-breeder birds, which will be transmitted to progeny.